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Toxicology. 2017 Dec 1;392:22-31. doi: 10.1016/j.tox.2017.10.005. Epub 2017 Oct 6.

Experimental oral iron administration: Histological investigations and expressions of iron handling proteins in rat retina with aging.

Author information

1
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: pankajkumar4020@gmail.com.
2
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: tapas_nag@yahoo.com.
3
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: jha9a@yahoo.co.in.
4
Department of Biochemistry, Delhi University South Campus, New Delhi 110021, India. Electronic address: sanjaydey@south.du.ac.in.
5
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: poorti88@gmail.com.
6
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: mmmnkshi@gmail.com.
7
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: clgtheboss@gmail.com.
8
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: jagriti2012@gmail.com.
9
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: tarasankar@hotmail.com.
10
Department of Anatomy, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: shashiwadhwa@hotmail.com.

Abstract

Iron is implicated in age-related macular degeneration (AMD). The aim of this study was to see if long-term, experimental iron administration with aging modifies retinal and choroidal structures and expressions of iron handling proteins, to understand some aspects of iron homeostasis. Male Wistar rats were fed with ferrous sulphate heptahydrate (500mg/kg body weight/week, oral; elemental iron availability: 20%) from 2 months of age onward until they were 19.5 month-old. At 8, 14 and 20 months of age, they were sacrificed and serum and retinal iron levels were detected by HPLC. Oxidative stress was analyzed by TBARS method. The retinas were examined for cell death (TUNEL), histology (electron microscopy) and the expressions of transferrin, transferrin receptor-1 [TFR-1], H- and L-ferritin. In control animals, at any age, there was no difference in the serum and retinal iron levels, but the latter increased significantly in 14- and 20 month-old iron-fed rats, indicating that retinal iron accumulation proceeds with progression of aging (>14 months). The serum and retinal TBARS levels increased significantly with progression of aging in experimental but not in control rats. There was significant damage to choriocapillaris, accumulation of phagosomes in retinal pigment epithelium and increased incidence of TUNEL+ cells in outer nuclear layer and vacuolation in inner nuclear layer (INL) of 20 month-aged experimental rats, compared to those in age-matched controls. Vacuolations in INL could indicate a long-term effect of iron accumulation in the inner retina. These events paralleled the increased expression of ferritins and transferrin and a decrease in the expression of TFR-1 in iron-fed rats with aging, thereby maintaining iron homeostasis in the retina. As some of these changes mimic with those happening in eyes with AMD, this model can be utilized to understand iron-induced pathophysiological changes in AMD.

KEYWORDS:

Choriocapillaris; Histopathology; Iron homeostasis; Photoreceptors; Retina

PMID:
28993186
DOI:
10.1016/j.tox.2017.10.005
[Indexed for MEDLINE]

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