Sunday, May 4, 2025
5/4/2025
Neuroprotection of retinal ganglion cells. - Project Summary Mitochondrial dysfunction contributes to the death of retinal ganglion cells and their axons in a variety of neurodegenerative conditions, including glaucoma, diabetic retinopathy, and traumatic optic neuropathy. Retinal ganglion cells are particularly vulnerable to dysfunction because the cells have high metabolic demands and axons that are prone to damage as they exit the eye. Under normal conditions, ganglion cells require an abundance of ATP to maintain cellular membrane potential, regulate calcium levels, and to remove glutamate from synapses; these demands increase when exposed to oxidative stress. A proposed treatment to manage oxidative stress following trauma to the optic nerve is administration of compounds to support mitochondrial function. Our laboratory has identified a high-density aromatic peptide (HDAP2) that targets cardiolipin on the inner mitochondrial membrane and optimizes the mitochondrial membrane potential under conditions of oxidative stress. We propose to study the effect of HDAP2 in adult mice following optic nerve crush on the survival of retinal ganglion cells, their dendritic arbors and the morphology of mitochondria within affected neurons. Optic nerve crush closely approximates the partial loss of optic nerve function and secondary loss of retinal ganglion cells observed in many neurodegenerative diseases (Goldblum and Mittag, 2002; Levkovitch-Verbin et al., 2000) and allows study of both primary and secondary effects of the trauma. Our preliminary results have shown that administration of HDAP2 following optic nerve crush significantly increases the survival of retinal ganglion cells following the procedure, demonstrating its potential for preserving neuronal function.
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