Combinatorial Therapeutic Strategy of Stem Cell Retinal Organoids and Neurotropic Factor for Glaucoma

Purpose: Glaucoma is a group of optic neuropathies characterized by retinal ganglion cell (RGC) death and visual field loss. A degenerative mechanism associated with RGC disrupted delivery neurotropic factors due to glaucomatous axonal damage. This transport critical for protection long-term neuronal function. Thus, we investigate potential therapeutic target, human Neuritin 1 (NRN1), which has demonstrated neuroprotective effects in rodent injury models. Further, the advent induced pluripotent stem (iPSC) technology allows iPSC-RGCs be generated in-vitro from commercial iPSCs reprogrammed corneal fibroblasts. We hypothesize NRN1 transplantation will sustain survival RGCs ultimately slow progression glaucoma-induced our ocular translaminar autonomous system (TAS) perfusion model system. allow us analyze approach both early-stage glaucoma (NRN1 therapy) protect dying RGCs, late-stage (iPSC-RGCs), when most are lost.
 Methods: Human donor eyes were obtained eye banks according Declaration Helsinki. The transfected AAV2-GFP seeded into posterior cups cultured TAS under pressurized conditions 2 days. Survival iPSC-RGCs, gliotic fibrotic pathways measured through expression qRT-PCR immunohistochemistry. Retinal function post-treatment was electroretinogram analysis.
 Results: successfully maintained differentials In contrast controls, observed increased after combination therapy iPSC-RGC. Additionally, found differential gene apoptosis, inflammation, markers.
 Conclusion: Our study identified that conjunction iPSC-RGC treatment promotes conditions. suggests could utilized as save neurons prevent neurodegeneration patients.