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Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3644-3651. doi: 10.1167/iovs.19-27079.

Rescue of M-cone Function in Aged Opn1mw-/- Mice, a Model for Late-Stage Blue Cone Monochromacy.

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Department of Ophthalmology, University of Florida, Gainesville, Florida, United States.
Department of Ophthalmology, John A. Moran Eye Center, University of Utah Health Science Center, Salt Lake City, Utah, United States.
Department of Neurobiology and Anatomy, University of Utah Health Science Center, Salt Lake City, Utah, United States.
Department of Biology, University of Utah, Salt Lake City, Utah, United States.



Previously we showed that AAV5-mediated expression of either human M- or L-opsin promoted regrowth of cone outer segments and rescued M-cone function in the treated M-opsin knockout (Opn1mw-/-) dorsal retina. In this study, we determined cone viability and window of treatability in aged Opn1mw-/- mice.


Cone viability was assessed with antibody against cone arrestin and peanut agglutinin (PNA) staining. The rate of cone degeneration in Opn1mw-/- mice was quantified by PNA staining. AAV5 vector expressing human L-opsin was injected subretinally into one eye of Opn1mw-/- mice at 1, 7, and 15 months old, while the contralateral eyes served as controls. M-cone-mediated retinal function was analyzed 2 and 13 months postinjection by full-field ERG. L-opsin transgene expression and cone outer segment structure were examined by immunohistochemistry.


We showed that dorsal M-opsin dominant cones exhibit outer segment degeneration at an early age in Opn1mw-/- mice, whereas ventral S-opsin dominant cones were normal. The remaining M-opsin dominant cones remained viable for at least 15 months, albeit having shortened or no outer segments. We also showed that AAV5-mediated expression of human L-opsin was still able to rescue function and outer segment structure in the remaining M-opsin dominant cones when treatment was initiated at 15 months of age.


Our results showing that the remaining M-opsin dominant cones in aged Opn1mw-/- mice can still be rescued by gene therapy is helpful for establishing the window of treatability in future blue cone monochromacy clinical trials.

[Indexed for MEDLINE]
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