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Published on: December 22, 2014
The Degeneration and Apoptosis Patterns of Cone Photoreceptors in rd11 Mice
Hua Zhang1, Xia Li2, Xufeng Dai1
1School of Ophthalmology & Optometry, The Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Abstract:
The retinal degeneration 11 (rd11) mouse is a new animal model with rapid photoreceptor degeneration. The long-term efficacy of gene therapy has a direct relationship with the onset of photoreceptor degeneration or apoptosis, whereas the degeneration or apoptosis patterns of photoreceptors are still unclear in rd11 mice. The distribution patterns of cone function-related L- and S-opsin were examined by immunofluorescence staining, and the apoptosis was performed by TUNEL assay in rd11 mice. The expression pattern of L-opsin or S-opsin in rd11 retina at postnatal day (P) 14 was similar to the pattern observed in wildtype retina. With increasing age, the expression of L-opsin and S-opsin, especially S-opsin, decreased significantly in rd11 mice. The degeneration of L-opsin began around the optic nerve and expanded to the periphery of the retina, from the ventral/nasal to dorsal/temporal retina, whereas the expression of S-opsin gradually decreased from the dorsal/temporal to ventral/nasal retina. Apoptotic signal appeared at P14 and was strongest at P28 of rd11 mice. The key genes associated with apoptosis confirmed those changes. These indicated that the degeneration and apoptosis of cone photoreceptors began at P14 of rd11 mice, which was a key point for gene therapy.
Insights
The rd11 mouse model shows rapid cone photoreceptor degeneration starting at postnatal day 14. This early onset is a critical window for potential gene therapy interventions.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- The rd11 mouse is a novel model for rapid photoreceptor degeneration.
- Understanding photoreceptor degeneration patterns is crucial for effective gene therapy, but remains unclear in rd11 mice.
Purpose of the Study:
- To investigate the temporal and spatial patterns of cone photoreceptor degeneration and apoptosis in rd11 mice.
- To identify the onset of degeneration as a potential therapeutic window for gene therapy.
Main Methods:
- Immunofluorescence staining was used to examine L- and S-opsin distribution.
- TUNEL assay was performed to detect apoptosis.
- Key apoptosis-associated genes were analyzed.
Main Results:
- L- and S-opsin expression patterns were initially similar to wildtype at postnatal day 14.
- Significant decreases in L- and S-opsin expression, particularly S-opsin, were observed with age.
- Degeneration initiated around the optic nerve and progressed peripherally, with distinct spatial patterns for L- and S-opsin.
- Apoptotic signals appeared at postnatal day 14 and peaked at postnatal day 28.
- Gene expression analysis confirmed apoptotic changes.
Conclusions:
- Cone photoreceptor degeneration and apoptosis in rd11 mice commence around postnatal day 14.
- This early onset highlights postnatal day 14 as a critical time point for considering gene therapy in this model.
