Changes in dopaminergic cells during progression of retinal degeneration

Program Number: 4164 Poster Board Number: A0169 Presentation Time: 8:30 AM–10:15 AM Changes in dopaminergic cells during progression of retinal degeneration Elena Ivanova1, 2, Botir Sagdullaev1, 2. 1Ophthalmology, Weill Medical College of Cornell University, New York, NY; 2Burke Medical Research Institute, White Plains, NY. Purpose: In the retina, dopamine is released by a single type of interplexiform neuron, dopaminergic amacrine cells (DACs). In the healthy retina, dopamine release is increased during light onset and triggers multiple changes associated with light adaptation, including modulation of gap junctions. Progressive photoreceptor cell loss during retinal degeneration (RD) leads to altered lightdriven input to DACs. However, structural and functional changes in DACs during RD remain unclear. The aim of this study was to determine anatomical changes in DACs during the course of retinal photoreceptor degeneration in murine models of retinitis pigmentosa. Methods: The retinas of rd1, rd10, and wt mice at P30, P60, and P120 were fixed and processed for immunohistochemistry and confocal microscopy. The dopaminergic cells were indirectly labeled for tyrosine hydroxylase (the key enzyme in dopamine production) and vesicular monoamine transporter 2 (responsible for dopamine uptake into synaptic vesicles). The densities and processes of DACs, and the distribution of the dopamine transporter, were quantified at identified retinal poles and eccentricities across different age groups. Results: In advanced stages of retinal degeneration, the number of retinal DACs was similar between wt and rd10 mice but was significantly decreased in rd1 mice. The densities of the dopaminergic processes in the inner plexiform layer (IPL) were highest in wt retinas, followed by rd10, and were significantly lower in rd1 mice. The number of the characteristic varicosities formed by dopaminergic processes in the IPL, which express dopamine transporter, was also diminished in RD retinas. Conclusions: The densities and fine anatomical features of DACs are affected during the course of retinal degeneration. These changes might correlate with the function of these amacrine cells and indicate modified dopamine release/uptake in the degenerated retina. Alterations in the dopaminergic system can cause changes in retinal light adaption status and lead to abnormal coupling of the neurons in the degenerated retina, contributing to dystrophic neuronal activity. Commercial Relationships: Elena Ivanova, None; Botir Sagdullaev, None Support: EY020535