Summary
This thesis evaluates two mouse models for RPE transplantation therapy in AMD, finding that the rd12 mouse (rpe65 mutation) is more suitable than sodium iodate models due to slower degeneration and partial functional rescue with chromophore supplementation and hESC-RPE transplantation. Notably, melanopsin-mediated pupillary light reflex was significantly impaired in rd12 mice and substantially restored by synthetic chromophore or subretinal rpe65 gene therapy, highlighting the RPE's critical role in supporting non-visual light responses relevant to circadian photoentrainment.
Key Findings
- Melanopsin labelling and function were significantly reduced in rd12 mice lacking functional rpe65.
- Synthetic chromophore supplementation significantly restored the intrinsic pupillary light reflex (iPLR) in rd12 mice.
- Subretinal (but not intravitreal) delivery of rpe65 gene therapy improved melanopsin function, implicating RPE-specific expression as necessary for non-visual photoreception rescue.
- hESC-RPE transplantation showed partial retinal function rescue in rd12 mice, but no surviving grafted cells were detected in the retina.
- Sodium iodate model caused severe loss of outer-retinal photoreceptor function that could not be restored by hESC-RPE transplantation, making it unsuitable for transplantation studies.
Categories
Eye Health & Vision: Investigates retinal pigment epithelium (RPE) transplantation models for AMD and retinal degeneration, with implications for restoring photoreceptor and visual function.
The Science of Light: Examines melanopsin function and the intrinsic pupillary light reflex (iPLR) in the context of RPE dysfunction and rpe65 mutation, providing mechanistic insight into non-visual photoreception.
Author(s)
A Lynch
Publication Year
2018
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