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1.
Bull Cancer. 2019 Dec;106(12):1160-1176. doi: 10.1016/j.bulcan.2019.09.008. Epub 2019 Nov 19.

Radiation induced optic neuropathy: Does treatment modality influence the risk?

Author information

1
Sohag University, Sohag University Hospital, Department of Clinical Oncology, Sohag East, 82524 Sohag, Egypt.
2
Croix-Rousse University Hospital, Department of Ophthalmology, 103, grande rue de la Croix-Rousse, Lyon, France; UMR-CNRS 5510, Mateis, Villeurbanne, Lyon, France.
3
Centre de Haute Énergie (CHE), 10, boulevard Pasteur, 06000 Nice, France. Electronic address: rjbensad@gmail.com.
4
Centre François-Baclesse/ARCHADE, Department of Radiation Oncology, 3, avenue General Harris, 14000 Caen, France; Unicaen - Normandie Université, laboratoire de physique corpusculaire IN2P3/ENSICAEN - UMR6534, boulevard du Marechal Juin, 14050 Caen, France.

Abstract

Radiation induced optic neuropathy (RION) is a rare but disastrous complication of radiation therapy in treatment of periorbital tumors. The objective of this study is to investigate the incidence of RION in series of patients treated from peri orbital tumors by recent photon and proton irradiation modalities. We searched the Pub Med database for studies in periorbital tumors including base of skull, sinonasal, pituitary, nasopharyngeal tumors and craniopharyngioma treated with Intensity modulated radiotherapy (IMRT) and with proton beam therapy (PBT) between 1992 and 2017 excluding metastatic tumors, lymphomas, pediatric series, those treated mainly with chemotherapy, target therapy and those written in languages other than English and French. The result retrieved 421 articles that were revised by the panel. Fourteen articles with IMRT and 27 with PBT reported usable data for the review from which 31studies that had pointed to the doses to the optic nerve (ON) and/or optic chiasm (OC) and incidence of RION have been analyzed. We have found that the incidence of RION had been reported fairly in both modalities and many other factors related to the patient, tumor, and irradiation process interplay in its development. We have concluded that proper treatment planning, good selection of treatment modality, adherence to dose constraints applied to critical structures all along with regular oncological and ophthalmological follow up, control of co-morbidities and early intervention, could help reducing its magnitude.

KEYWORDS:

IMRT; Proton beam therapy; RION

PMID:
31757405
DOI:
10.1016/j.bulcan.2019.09.008
[Indexed for MEDLINE]
Icon for Elsevier Science
2.
Undersea Hyperb Med. 2019 Sep - Dec - Fourth Quarter;46(5):709-712.

Acute direct traumatic optic neuropathy treated with steroids, minocycline and hyperbaric oxygen: a case report.

Author information

1
Department of Ophthalmology and Pediatrics, University of Maryland School of Medicine U.S.
2
Department of Ophthalmology Residency, University of Maryland Medical Center U.S.
3
Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland U.S.

Abstract

We describe the emergency management of a man who experienced acute vision loss diagnosed as direct traumatic optic neuropathy (TON) in his right eye (no light perception) after falling from a height. TON is caused by a high-impact mechanism of injury. Clinical findings include acute vision loss, which is typically immediate, afferent pupillary defect, decreased color vision, and visual field defects. Treatment is controversial because of the lack of strong evidence supporting intervention over observation. In this case report, our treatment strategy comprised immediate hyperbaric oxygen (HBO2) and daily high doses of a steroid. On the second day, minocycline was added to the treatment regimen for its neuroprotective effects. The patient was discharged after receiving six HBO2 treatments and six days of intravenous solumedrol transitioned to oral prednisone. After the third HBO2 treatment, his vision improved to 20/100; after the fourth treatment, it was 20/40 and plateaued. At the time of discharge, it was 20/40. At two-month follow-up, his corrected visual acuity was 20/60+2 in the affected eye. Immediate HBO2 for ischemic and mechanical injury to the optic nerve following trauma is a therapeutic option.

KEYWORDS:

acute vision loss; hyperbaric oxygen therapy ; ocular trauma ; ophthalmologic trauma

PMID:
31683371
[Indexed for MEDLINE]
3.
J Craniofac Surg. 2019 Oct;30(7):e683-e687. doi: 10.1097/SCS.0000000000005892.

Orbital Decompression for Treatment of Acute Visual Loss After Facial Trauma.

Author information

1
Department of General Surgery.
2
Plastic and Reconstructive Surgery, Kendall Regional Medical Center, Miami, FL.

Abstract

Injury to the orbital region represents a significant proportion of emergency department attendances and it is a common injury in patients with multisystem trauma. To date, trauma remains a leading cause of monocular blindness.Traumatic optic neuropathy may be caused by direct trauma to the optic nerve and from compression caused by foreign bodies and bone fragments. Indirect trauma can lead to visual loss from transmitted force to the optic canal by blunt facial trauma without associated fractures. Occasionally traumatic optic neuropathy is due to reversible changes, such as edema or contusion.High-dose intravenous steroids and surgical decompression of the optic canal have been advocated for the management of acute traumatic optic neuropathy, but the efficacy and safety of these treatments have been questioned.The authors present 3 patients with traumatic optic nerve injury, 1 due to a gunshot wound to the face and 2 caused by blunt facial trauma, where fragments of bone intrude into the orbit leading to compression of its content. These injuries where successfully treated with both preoperative intravenous steroids followed by acute surgical decompression of the orbit with return of visual function.

PMID:
31503126
DOI:
10.1097/SCS.0000000000005892
[Indexed for MEDLINE]
Icon for Wolters Kluwer
4.
BMC Surg. 2019 Jul 4;19(1):76. doi: 10.1186/s12893-019-0536-2.

An unusual case of intra orbital foreign body; diagnosis, management, and outcome: a case report.

Author information

1
Department of Neurosurgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
2
Trauma Surgery, Department of General and Vascular Surgery, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran.
3
School of Medicine, Mercer University, Savannah, GA, USA.
4
Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran. sinaparsa91@gmail.com.

Abstract

BACKGROUND:

An orbitocranial injury with a penetrating Intraorbital Foreign Body (IOFB) is listed as a rare cause of penetrating trauma. Since this type of trauma is considered a surgical emergency, taking a thorough history along with careful examination to find out the mechanism and cause of the trauma is crucial towards correct diagnosis and management of the disease.

CASE PRESENTATION:

A 35-year-old male patient was presented to the ER with an occupational craniofacial injury because of an IOFB. The patient underwent an extra-dural orbitocranial craniotomy procedure to remove the foreign body. Interestingly, a plastic foreign body (a piece of a plastic pipe) was removed from the orbital cavity, which was suspected to be a fractured orbital bone, at first place.

CONCLUSION:

In this study, we demonstrated that plastics could mimic bone structure in a Computerized Tomography (CT) scan leading to possible initial misdiagnosis. Hence high clinical suspicion is necessary for the correct diagnosis of such cases. However, despite the prompt intervention, our patient ended up with permanent vision loss in his injured eye.

KEYWORDS:

CT; Craniotomy; Head trauma; Intraorbital foreign body

PMID:
31272434
PMCID:
PMC6611006
DOI:
10.1186/s12893-019-0536-2
[Indexed for MEDLINE]
Free PMC Article
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5.
J Med Food. 2019 Aug;22(8):771-778. doi: 10.1089/jmf.2018.4350. Epub 2019 Jul 3.

Neuroprotective Effect of Ginkgo Biloba Extract Against Hypoxic Retinal Ganglion Cell Degeneration In Vitro and In Vivo.

Author information

1
1Department of Ophthalmology, Gyeongsang National University Changwon Hospital, Gyeongsang National University, School of Medicine, Changwon, Korea.
2
2Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

Hypoxia-induced oxidative stress and disturbed microvascular circulation are both associated with pathogenesis of glaucoma. Ginkgo biloba extract (GBE) has been reported to have positive pharmacological effects on oxidative stress and impaired vascular circulation. This study aimed to investigate the neuroprotective effect of GBE against hypoxic injury to retinal ganglion cells (RGCs) both in vitro and in vivo. The rat RGC line was used, and oxidative stress was induced by hydrogen peroxide (H2O2) in vitro. EGb 761, a standardized GBE, or vehicle was applied to RGCs. Hypoxic optic nerve injury in vivo was induced by clamping the optic nerve of rats with a "microserrefine clip" with an applicator, which was applied without crushing the optic nerve. This method is different from "optic nerve crush model" and does not involve elevation of intraocular pressure, and may serve as a possible normal tension glaucoma animal model. EGb 761 at various concentrations or vehicle was administered intraperitoneally. RGC density was measured to estimate the survival both in vitro and in vivo. The survival of RGCs was significantly (P < .001) higher upon treatment with 1 or 5 μg/mL of EGb 761 compared with vehicle after oxidative stress in vitro. RGC density upon treatment with EGb 761 of 100 mg/kg (1465.6 ± 175 cells/mm2) or 250 mg/kg (1307.6 ± 213 cells/mm2) was significantly higher (P < .01, P < .05, respectively) than that obtained with vehicle (876.3 ± 136 cells/mm2) in vivo. Our results suggest that GBE has neuroprotective effect on RGCs against hypoxic injury both in vitro and in vivo.

KEYWORDS:

PMID:
31268403
DOI:
10.1089/jmf.2018.4350
[Indexed for MEDLINE]
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6.
Neuron. 2019 Aug 21;103(4):642-657.e7. doi: 10.1016/j.neuron.2019.05.044. Epub 2019 Jun 26.

Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells.

Author information

1
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
2
Department of Physiology & Biophysics, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
3
Department of Neurobiology, Northwestern University, Evanston, IL, USA.
4
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
5
Department of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: kpark@miami.edu.

Abstract

Neuronal subtypes show diverse injury responses, but the molecular underpinnings remain elusive. Using transgenic mice that allow reliable visualization of axonal fate, we demonstrate that intrinsically photosensitive retinal ganglion cells (ipRGCs) are both resilient to cell death and highly regenerative. Using RNA sequencing (RNA-seq), we show genes that are differentially expressed in ipRGCs and that associate with their survival and axon regeneration. Strikingly, thrombospondin-1 (Thbs1) ranked as the most differentially expressed gene, along with the well-documented injury-response genes Atf3 and Jun. THBS1 knockdown in RGCs eliminated axon regeneration. Conversely, RGC overexpression of THBS1 enhanced regeneration in both ipRGCs and non-ipRGCs, an effect that was dependent on syndecan-1, a known THBS1-binding protein. All structural domains of the THBS1 were not equally effective; the trimerization and C-terminal domains promoted regeneration, while the THBS type-1 repeats were dispensable. Our results identify cell-type-specific induction of Thbs1 as a novel gene conferring high regenerative capacity.

KEYWORDS:

axon growth; axon injury; axon regeneration; extracellular matrix protein; ipRGCs; melanopsin; retina; retinal ganglion cells; syndecan; thrombospondin

PMID:
31255486
PMCID:
PMC6706310
[Available on 2020-08-21]
DOI:
10.1016/j.neuron.2019.05.044
[Indexed for MEDLINE]
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7.
BMC Med Imaging. 2019 Jun 18;19(1):49. doi: 10.1186/s12880-019-0347-z.

Magnetic resonance imaging indicator of the causes of optic neuropathy in IgG4-related ophthalmic disease.

Author information

1
Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
2
Department of Ophthalmology, PLA Army General Hospital, No.5, nanmencang, Dongsishitiao, dongcheng district, Beijing, 100000, China.
3
Department of Rheumatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
4
Department of Ophthalmology, PLA General Hospital, No.28, fuxing road, haidian district, Beijing, China, 100080.
5
Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong'an Road, Xicheng District, Beijing, 100050, People's Republic of China. faraway_sweet@163.com.

Abstract

BACKGROUND:

The following study investigates the involvement of optic neuropathy in IgG4-related ophthalmic diseases (IgG4-ROD) based on the magnetic resonance imaging (MRI) data, and different imaging features of IgG4-ROD related optic neuropathy related to other orbital diseases.

METHODS:

This retrospective study included 225 patients with IgG4-RD admitted at two ophthalmology centers between January 2014 and December 2017. Twenty-six patients had both pre-therapeutic orbital MRI and optic never injury. The causes of optic neuropathy were analyzed, and the special sign in MRI to diagnose IgG4-ROD was also evaluated.

RESULTS:

Twelve cases had inflammation of the optic nerve sheath, while 14 cases had compression due to extraocular muscles and pseudo tumor masses. Two cases had hypertrophic cranial pachymeningitis, while one case had hypophysis involving optic chiasma.

CONCLUSION:

The most common causes of optic nerve injury in IgG-4 ROD are inflammation of optic nerve sheath, compression of extraocular muscles, pseudo tumor mass and hypertrophic cranial pachymeningitis, and hypophysis involving optic chiasma.

KEYWORDS:

Cause of disease; IgG4-related ophthalmic disease; Magnetic resonance imaging; Optic neuropathy

PMID:
31215395
PMCID:
PMC6582478
DOI:
10.1186/s12880-019-0347-z
[Indexed for MEDLINE]
Free PMC Article
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8.
Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2380-2387. doi: 10.1167/iovs.19-26683.

Tau Is Involved in Death of Retinal Ganglion Cells of Rats From Optic Nerve Crush.

Author information

1
Department of Ophthalmology, Osaka Medical College, Osaka, Japan.

Abstract

Purpose:

To determine whether tauopathies are associated with impaired autophagy and involved in the death of retinal ganglion cells (RGCs) of rats from an optic nerve crush (ONC).

Methods:

Short interfering RNA (siRNA) of the tau gene (si-Tau) or nontargeting siRNA (si-NC) was injected intravitreally 48 hours prior to ONC. The effects of silencing the tau gene on neuroprotection were determined by the number of Tuj-1-stained RGCs on days 7 and 14 after the ONC. The changes in the expressions of phosphorylated tau, P62, and LC3B were determined by immunoblots and immunohistochemistry on day 7.

Results:

Autophagy was impaired in the retina on day 7 after the ONC as the P62 level increased by 3.1-fold from the sham control level with a reduction in the ratio LC3B2/LC3B1. There was a 2.1-fold increase of phosphorylated tau (ser 396) in the retina, and si-Tau depressed the increase by 1.3-fold (n = 3 each). The expressions of tau and P62 were well colocalized. They were observed in the somas of RGCs and retinal nerve fibers (RNFs), and these expressions were increased after the ONC. Pretreatment by si-Tau showed significant protection in the number of RGCs after the ONC. Specifically, the density of RGCs was 540 ± 74.5 cells/mm2 on day 14 in the si-NC group, while the level was maintained at 1321 ± 192 cells/mm2 in the si-Tau group (n = 4 each).

Conclusions:

Silencing the tau gene is neuroprotective, and tauopathies may be involved in the death of RGCs after ONC. Impaired autophagy may be involved in ONC-induced tauopathies.

PMID:
31141609
DOI:
10.1167/iovs.19-26683
[Indexed for MEDLINE]
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9.
Neuron. 2019 Jul 3;103(1):39-51.e5. doi: 10.1016/j.neuron.2019.04.033. Epub 2019 May 20.

Elevating Growth Factor Responsiveness and Axon Regeneration by Modulating Presynaptic Inputs.

Author information

1
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA, USA.
2
F.M. Kirby Neurobiology Center, Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA, USA; Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: prwillia@wustl.edu.
3
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
4
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; United States Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA.

Abstract

Despite robust effects on immature neurons, growth factors minimally promote axon regeneration in the adult central nervous system (CNS). Attempting to improve growth-factor responsiveness in mature neurons by dedifferentiation, we overexpressed Lin28 in the retina. Lin28-treated retinas responded to insulin-like growth factor-1 (IGF1) by initiating retinal ganglion cell (RGC) axon regeneration after axotomy. Surprisingly, this effect was cell non-autonomous. Lin28 expression was required only in amacrine cells, inhibitory neurons that innervate RGCs. Ultimately, we found that optic-nerve crush pathologically upregulated activity in amacrine cells, which reduced RGC electrical activity and suppressed growth-factor signaling. Silencing amacrine cells or pharmacologically blocking inhibitory neurotransmission also induced IGF1 competence. Remarkably, RGCs regenerating across these manipulations localized IGF1 receptor to their primary cilia, which maintained their signaling competence and regenerative ability. Thus, our results reveal a circuit-based mechanism that regulates CNS axon regeneration and implicate primary cilia as a regenerative signaling hub.

PMID:
31122676
DOI:
10.1016/j.neuron.2019.04.033
[Indexed for MEDLINE]
Icon for Elsevier Science
10.
Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2005-2011. doi: 10.1167/iovs.18-26094.

Indirect Traumatic Optic Neuropathy in Mild Chronic Traumatic Brain Injury.

Author information

1
Department of Ophthalmology, University of Arizona College of Medicine, Phoenix, Arizona, United States.
2
Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, United States.
3
Department of Neurology, University of California, San Francisco, School of Medicine, San Francisco, California, United States.
4
Associated Retinal Consultants, Phoenix, Arizona, United States.
5
Heidelberg Engineering, Inc., Franklin, Massachusetts, United States.

Abstract

Purpose:

To analyze the clinical presentation and optical coherence tomography (OCT) findings in indirect traumatic optic neuropathy (ITON) in veterans with chronic mild traumatic brain injury (mTBI).

Methods:

This retrospective study is the first to describe the OCT pattern of subclinical to mild ITON in veterans with chronic mTBI. The thicknesses of the macular ganglion cell layer (mGCL), peripapillary retinal nerve fiber layer (pRNFL), and subfoveal choroidal layer were analyzed in young veterans who had mTBI of >6 months' duration and either blunt head injury or improvised explosive device (IED) concussions.

Results:

Three major OCT findings were demonstrated: (1) temporal pRNFL thinning was associated with subclinical TON in the eyes of chronic mTBI patients compared with controls; within mTBI subjects, nasal mGCL thinning at the 3-mm modified Early Treatment Diabetic Retinopathy Study circle diameter distance from the fovea correlated with the corresponding temporal retinal nerve fiber layer thinning; (2) inner (1 mm) superior thinning was greater than that of the temporal mGCL in blunt head injury and could potentially distinguish it from IED concussive head trauma; and (3) subfoveal choroidal thinning was significantly worse in eyes of mTBI patients compared with those of controls.

Conclusions:

These OCT findings may contribute to the understanding of the spectrum of visual injuries resulting from head trauma.

PMID:
31067321
DOI:
10.1167/iovs.18-26094
[Indexed for MEDLINE]
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11.
Invest Ophthalmol Vis Sci. 2019 May 1;60(6):1987-1995. doi: 10.1167/iovs.18-26333.

Ocular Effects of Sildenafil in Naïve Mice and a Mouse Model of Optic Nerve Crush.

Author information

1
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
2
Department of Ophthalmology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
3
The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel.
4
Department of Ophthalmology, Shaare Zedek Medical Center, Jerusalem, Israel.
5
Faculty of Medicine, Hebrew University Medical Center, Jerusalem, Israel.
6
Department of Ophthalmology, Bnai Zion Medical Center, Haifa, Israel.
7
Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

Abstract

Purpose:

To investigate the potential neuroprotective effect of sildenafil on the ocular circulation in mice with/without optic nerve crush (ONC).

Methods:

Male adult mice (n = 63) were treated with intravitreal (IVT) sildenafil 24 μg/3 μL, intraperitoneal (IP) sildenafil 24 μg/300 μL, or IP saline immediately before right ONC induction (ONC group). A second group (n = 123) received the same treatments without ONC induction (naïve group). Evaluations included fluorescein angiography (naïve group; day 0), molecular studies (days 1 and 3), and retinal and optic nerve histology (day 21).

Results:

Maximal retinal vessel dilatation and increased choroidal effusion were detected within 30 minutes of sildenafil injection. In the ONC group, moderate retinal ganglion cell (RGC) loss was noted at 21 days. However, molecular studies showed increased stress induced gene expression (IP superoxide dismutase [SOD]-1: 3.1-fold; heme oxygenase [HO]-1: 5.8-fold; IVT SOD-1: 1.47-fold), proapoptotic gene expression (IP BAX/B-cell lymphoma [BCL]-2 10.8-/2.3-fold), and glial gene expression (IP glial fibrillary acidic protein [GFAP]: 2.8- and myelin basic protein [MBP]: 2.5-fold). In the naïve group, IVT sildenafil was not associated with RGC loss or optic nerve stroke on histology, although in two samples, molecular parameters were compatible with stroke, showing increased gene expression of HO-1 (3.8-fold) and BCL-2 (2.5-fold). In the IP sildenafil subgroup, optic neuropathy was observed in 6/120 optic nerves, including 3 cyan fluorescence protein (CFP)-Thy-1 mice. Levels of antiapoptosis and anti-ischemia genes were decreased (<0.5-fold) except for three outliers.

Conclusions:

Sildenafil affects retinal and choroidal perfusion in mice. When injected immediately before ONC, molecular parameters showed a preconditioning neuroprotective effect while histologic studies did not. In the absence of ONC, it is associated with neuropathy, possibly dose-dependent.

PMID:
31063183
DOI:
10.1167/iovs.18-26333
[Indexed for MEDLINE]
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12.
Mol Med Rep. 2019 Jun;19(6):4863-4871. doi: 10.3892/mmr.2019.10151. Epub 2019 Apr 11.

Caffeic acid phenethyl ester attenuates nuclear factor‑κB‑mediated inflammatory responses in Müller cells and protects against retinal ganglion cell death.

Author information

1
Eye Institute, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China.
2
Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China.

Abstract

Glaucoma is characterized by the death of retinal ganglion cells (RGCs) and visual field defects, and is a leading cause of blindness worldwide. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic found in propolis from honeybee hives, can inhibit the activation of nuclear factor κ light‑chain‑enhancer of activated B cells (NF‑κB) and has therapeutic potential in inflammatory disease. The present study used a rat model of optic nerve crush (ONC) injury to investigate the effect of CAPE on glaucoma. The death of RGCs at day 14 was significantly reduced in CAPE‑treated animals compared with the non‑treated group according to Brn3a and TUNEL staining. In addition, CAPE decreased the severity of inflammation in the retina, reflected by the decreased expression of inflammatory cytokines, including interleukin (IL)‑8, IL‑6, inducible nitric oxide synthase, cycloooxygenase‑2, tumor necrosis factor‑α and chemokine C‑C ligand‑2, in CAPE‑treated rats. The hypertrophy of astrocytes and Müller cells (gliosis) caused by ONC was also found to be attenuated by CAPE, accompanied by the inhibition of NF‑κB signaling. Similarly, in vitro, CAPE suppressed the proliferation and migration of primary astrocytes induced by lipopolysaccharide, as well as the activation of NF‑κB. These results suggest that CAPE protected against RGC and attenuated inflammatory responses in a rat model of ONC by suppressing NF‑κB activation.

PMID:
31059064
PMCID:
PMC6522951
DOI:
10.3892/mmr.2019.10151
[Indexed for MEDLINE]
Free PMC Article
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13.
Nepal J Ophthalmol. 2018 Jul;10(20):196-202. doi: 10.3126/nepjoph.v10i2.20031.

Traumatic Luxation of the Eye Ball with Optic Nerve Transection Following Road Traffic Accident: Report of Two Cases and Brief Review of Literature.

Author information

1
Neuro Cardio and Multi Speciality Hospital, Biratnagar, Nepal.

Abstract

BACKGROUND:

Traumatic luxation of the eye ball is rare with only 106 cases reported in PubMed till date. The anatomic location of the eyeball within the socket and the resilience of the globe to pressure force, attachment to extraocular muscles and optic nerve prevents luxation during trauma.

CASE:

Road traffic accidents (RTA) is the most common cause for these injuries and the outcome can vary from complete recovery on repositioning to visual loss due to globe perforation or optic nerve injury. We report two unique cases of traumatic right globe luxation and complete optic nerve transection due to RTA and give a brief review of literature.

CONCLUSION:

RTA leading to eye ball luxation though rare can be a challenging situation when encountered. Given the limited time for the salvage of the eye early intervention is not always possible especially in developing countries where there is delay in reaching the hospital. Despite all these confounding factors attempt must be made to salvage the eye either for functional, cosmetic or psychological reasons.

PMID:
31056567
DOI:
10.3126/nepjoph.v10i2.20031
[Indexed for MEDLINE]
14.
PLoS One. 2019 May 2;14(5):e0209733. doi: 10.1371/journal.pone.0209733. eCollection 2019.

Application of CNTF or FGF-2 increases the number of M2-like macrophages after optic nerve injury in adult Rana pipiens.

Author information

1
Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, Old San Juan, Puerto Rico.
2
Department of Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Abstract

We have previously shown that a single application of the growth factors ciliary neurotrophic factor (CNTF) or fibroblast growth factor 2 (FGF-2) to the crushed optic nerve of the frog, Rana pipiens, increases the numbers and elongation rate of regenerating retinal ganglion cell axons. Here we investigate the effects of these factors on the numbers and types of macrophages that invade the regeneration zone. In control PBS-treated nerves, many macrophages are present 100 μm distal to the crush site at 1 week after injury; their numbers halve by 2 weeks. A single application of CNTF at the time of injury triples the numbers of macrophages at 1 week, with this increase compared to control being maintained at 2 weeks. Application of FGF-2 is equally effective at 1 week, but the macrophage numbers have fallen to control levels at 2 weeks. Immunostaining with a pan-macrophage marker, ED1, and a marker for M2-like macrophages, Arg-1, showed that the proportion of the putative M2 phenotype remained at approximately 80% with all treatments. Electron microscopy of the macrophages at 1 week shows strong phagocytic activity with all treatments, with many vacuoles containing axon fragments and membrane debris. At 2 weeks with PBS or FGF-2 treatment the remaining macrophages are less phagocytically active, containing mainly lipid inclusions. With CNTF treatment, at 2 weeks many of the more numerous macrophages are still phagocytosing axonal debris, although they also contain lipid inclusions. We conclude that the increase in macrophage influx seen after growth factor application is beneficial for the regenerating axons, probably due to more extensive removal of degenerating distal axons, but also perhaps to secretion of growth-promoting substances.

PMID:
31048836
PMCID:
PMC6507305
DOI:
10.1371/journal.pone.0209733
[Indexed for MEDLINE]
Free PMC Article
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15.
Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1748-1759. doi: 10.1167/iovs.18-26449.

Activation of the BMP4/Smad1 Pathway Promotes Retinal Ganglion Cell Survival and Axon Regeneration.

Author information

1
Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, United Kingdom.

Abstract

Purpose:

We investigate if the BMP4/Smad1 intracellular signaling pathway is neuroprotective and axogenic in adult rodent retinal ganglion cells (RGC) in vivo and in vitro.

Methods:

Adult retinal cultures were prepared from intact and after optic nerve crush (ONC) injured rats that have been stimulated to survive and regenerate using an intravitreal peripheral nerve (PN) graft. Laser capture microdissection (LCM) then was used to isolate RGC with and without neurites. Quantitative RT-PCR determined changes in BMP4/Smad1 signaling pathway mRNA. Immunohistochemistry confirmed localization of BMP4 and activation of Smad1 in ONC+PN-stimulated RGC in vivo. BMP4 peptide was used to stimulate RGC survival and neurite/axon regeneration in vitro and in vivo. Finally, the rapamycin sensitivity of the effects was determined in BMP4-stimulated RGC in vitro and in vivo.

Results:

In retinal cultures prepared from intact and ONC+PN-stimulated rats, RGC with neurites had upregulated regeneration-related and BMP4/Smad1 signaling pathway mRNA levels, while low levels of these mRNAs were present in RGC isolated without neurites. An optimal dose of 200 ng/mL BMP4 peptide in vitro promoted approximately 30% RGC survival and disinhibited RGC neurite outgrowth, despite the presence of inhibitory CNS myelin extracts. BMP4 also promoted approximately 30% RGC survival in vivo and stimulated significant RGC axon regeneration at 100, 200, and 400 μm beyond the lesion site. Finally, the response of RGC to BMP4 treatment in vitro and in vivo was rapamycin-insensitive.

Conclusions:

Activation of the BMP4/Smad1 pathway promotes survival and axon regeneration independent of mTOR and, therefore, may be of therapeutic interest.

PMID:
31022296
DOI:
10.1167/iovs.18-26449
[Indexed for MEDLINE]
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17.
Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1556-1565. doi: 10.1167/iovs.18-26441.

Optical Coherence Tomography Angiography in Mice: Quantitative Analysis After Experimental Models of Retinal Damage.

Author information

1
Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.
2
Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada.
3
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.

Abstract

Purpose:

We implemented optical coherence tomography angiography (OCT-A) in mice to: (1) develop quantitative parameters from OCT-A images, (2) measure the reproducibility of the parameters, and (3) determine the impact of experimental models of inner and outer retinal damage on OCT-A findings.

Methods:

OCT-A images were acquired with a customized system (Spectralis Multiline OCT2). To assess reproducibility, imaging was performed five times over 1 month. Inner retinal damage was induced with optic nerve transection, crush, or intravitreal N-methyl-d-aspartic acid injection in transgenic mice with fluorescently labeled retinal ganglion cells (RGCs). Light-induced retinal damage was induced in albino mice. Mice were imaged at baseline and serially post injury. Perfusion density, vessel length, and branch points were computed from OCT-A images of the superficial, intermediate, and deep vascular plexuses.

Results:

The range of relative differences measured between sessions across the vascular plexuses were: perfusion density (2.8%-7.0%), vessel length (1.9%-4.1%), and branch points (1.9%-5.0%). In mice with progressive RGC loss, imaged serially and culminating in around 70% loss in the fluorescence signal and 18% loss in inner retinal thickness, there were no measurable changes in any OCT-A parameter up to 4 months post injury that exceeded measurement variability. However, light-induced retinal damage elicited a progressive loss of the deep vascular plexus signal, starting as early as 3 days post injury.

Conclusions:

Vessel length and branch points were generally the most reproducible among the parameters. Injury causing RGC loss in mice did not elicit an early change in the OCT-A signal.

PMID:
30995294
DOI:
10.1167/iovs.18-26441
[Indexed for MEDLINE]
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18.
PLoS One. 2019 Apr 17;14(4):e0215297. doi: 10.1371/journal.pone.0215297. eCollection 2019.

Longitudinal evaluation of visual function and structure for detection of subclinical Ethambutol-induced optic neuropathy.

Author information

1
Department of Ophthalmology, Hallym University College of Medicine, Seoul, Republic of Korea.

Abstract

PURPOSE:

To longitudinally evaluate the visual function and structure of patients taking ethambutol by various modalities and identify useful tests for detection of subclinical ethambutol-induced optic toxicity.

METHODS:

This retrospective study enrolled 84 patients with newly diagnosed tuberculosis treated with ethambutol. Best-corrected visual acuity (BCVA), color vision, contrast sensitivity, fundus and retinal nerve fiber layer (RNFL) photography, automated visual field (VF) test, and optical coherence tomography (OCT) were performed: prior to starting; every month during administration, and 1 month after stoppage. We longitudinally compared visual function and structure with the baseline and identified the occurrence of subclinical toxicity.

RESULTS:

BCVA, color vision, and contrast sensitivity showed no change from the baseline. Mean temporal RNFL thickness was significantly increased at 6 months (p = 0.014). Subclinical toxicity was found in 22 eyes of 14 patients (i.e., 13% of 168 eyes), in the forms of VFI decrease (VF index, 9 eyes of 6 patients), quadrant RNFL thickness increase (5 eyes of 4 patients), and VF pattern defect (12 eyes of 6 patients). 73% of the patients showed recovery to the baseline at 1 month post-stoppage. The risk factors for occurrence of subclinical toxicity were age, cumulative dose, and medication duration.

CONCLUSION:

Mean temporal RNFL thickness increased after administration. The VFI, quadrant RNFL thickness, and VF pattern defect could prove useful in assessment of subclinical toxicity. Medication duration was shown to be a strong risk factor for occurrence of subclinical toxicity.

PMID:
30995284
PMCID:
PMC6469811
DOI:
10.1371/journal.pone.0215297
[Indexed for MEDLINE]
Free PMC Article
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19.
Biomed Pharmacother. 2019 Apr;112:108729. doi: 10.1016/j.biopha.2019.108729. Epub 2019 Mar 2.

Arbutin attenuates hydrogen peroxide-induced oxidative injury through regulation of microRNA-29a in retinal ganglion cells.

Author information

1
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, 450052, China.
2
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, 450052, China. Electronic address: wangwenzhan123@sina.com.

Abstract

BACKGROUND:

Optic nerve injury is a severe complication of traumatic brain injury, which may lead to permanent and potentially loss of vision. Arbutin (ARB) is a natural hydroquinone glycoside, has been widely utilized to treat pigmented disorders. However, the role of ARB in optic nerve injury is still unclear. The study attempted to explore the effect of ARB on H2O2-induced oxidative injury in RGCs.

METHODS:

RGCs were treated with different concentrations of H2O2 to construct a cell oxidative injury model. Subsequently, the effects of ARB on these injured cells were examined through testing cell viability, apoptosis and their associated factors. MicroRNA-29a (miR-29a) inhibitor was transfected into RGCs, and the regulatory effect of miR-29a inhibition on H2O2-injured cells was detected. Further, the important signaling pathways of MEK/ERK and p38MAPK were determined to uncover the underlying mechanism.

RESULTS:

We firstly used H2O2 to induce RGCs injury, and subsequent experiments found that ARB significantly alleviated H2O2-induced cell injury in RGCs by promoting cell viability, reducing apoptosis, and regulating the protein levels of cell growth-associated factors. Increasing expression of miR-29a was observed in ARB and H2O2 treated cells. Moreover, miR-29a inhibition significantly abrogated the protective effect of ARB on H2O2-injured RGCs. NRAS was predicated as a direct target gene of miR-29a. Mechanistically, ARB blocked MEK/ERK and p38MAPK pathways by up-regulating miR-29a.

CONCLUSIONS:

These data demonstrated that ARB protected RGCs against oxidative injury induced by H2O2 through blocking MEK/ERK and p38MAPK signaling pathways by up-regulation of miR-29a.

KEYWORDS:

Arbutin; MEK/ERK; Optic nerve injury; Oxidative injury; microRNA-29a; p38MAPK

PMID:
30970524
DOI:
10.1016/j.biopha.2019.108729
[Indexed for MEDLINE]
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20.
Int Immunopharmacol. 2019 Jun;71:313-320. doi: 10.1016/j.intimp.2019.03.029. Epub 2019 Mar 30.

The levels and significance of inflammasomes in the mouse retina following optic nerve crush.

Author information

1
Department of Ophthalmology, Daping Hospital and Institute of Surgery Research, Army Medical University, Chongqing, China.
2
Department of Ophthalmology, Xinqiao Hospital, Army Medical University, Chongqing, China.
3
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital and Research Institute of Surgery, Army Medical University, Chongqing, China.
4
Department of Ophthalmology, Xinqiao Hospital, Army Medical University, Chongqing, China. Electronic address: yuanrongdi@126.com.
5
Department of Ophthalmology, Daping Hospital and Institute of Surgery Research, Army Medical University, Chongqing, China. Electronic address: yejian1979@163.com.

Abstract

Inflammasomes play an important role in neuroinflammation. However, their function during the secondary death of retinal cells after traumatic optic neuropathy and their dependence on pathogen stimuli remains unclear. Therefore, we evaluated the expression profiles of 10 different inflammasome-related mRNAs in the retina following an optic nerve crush (OPC) injury under both conventional sterile as well as non-sterile conditions, and validated two significantly varied ones on a protein level. While most factors were much more highly elevated in non-sterile conditions, both Nlrp1b and Nlrp3 inflammasome mRNAs were increased significantly on postoperative day 1 to day 7 in the mouse sterile OPC injury model. While production of the inflammation-associated cytokines IL-1β and IL-18 could be continuously detected on an mRNA level postoperatively, a clear peak could be seen on day 7 that coincided with maximal expression of caspase-1 mRNA and with observation of retinal ganglion cells death, despite the mice being held in specific-pathogen free conditions. As such, the pro-inflammatory cytokines activated by inflammasome activation during OPC injury may drive secondary cell death through pyroptosis, and inhibition of these delayed responses may be an important means of preventing worsened injury and loss of vision in trauma patients.

KEYWORDS:

Inflammasomes; Neuroinflammation; Pyroptosis

PMID:
30939414
DOI:
10.1016/j.intimp.2019.03.029
[Indexed for MEDLINE]
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