Abstract
The rapid and massive degeneration of photoreceptors in retinal degeneration might have a dramatic negative effect on retinal circuits downstream of photoreceptors. However, the impact of photoreceptor loss on the morphology and function of retinal ganglion cells (RGCs) is not fully understood, precluding the rational design of therapeutic interventions that can reverse the progressive loss of retinal function. The present study investigated the morphological changes in several identified RGCs in the retinal degeneration rd1 mouse model of retinitis pigmentosa (RP), using a combination of viral transfection, microinjection of neurobiotin and confocal microscopy. Individual RGCs were visualized with a high degree of detail using an adeno-associated virus (AAV) vector carrying the gene for enhanced green fluorescent protein (EGFP), allowed for large-scale surveys of the morphology of RGCs over a wide age range. Interestingly, we found that the RGCs of nine different types we encountered were especially resistant to photoreceptor degeneration, and retained their fine dendritic geometry well beyond the complete death of photoreceptors. In addition, the RGC-specific markers revealed a remarkable degree of stability in both morphology and numbers of two identified types of RGCs for up to 18 months of age. Collectively, our data suggest that ganglion cells, the only output cells of the retina, are well preserved morphologically, indicating the ganglion cell population might be an attractive target for treating vision loss.
Highlights
The eye provides vision that relies on the integrity of cellular structures and functions of the retina
We explored the feasibility of using an associated virus (AAV) vector carrying a gene encoding enhanced green fluorescent protein (EGFP) as a reliable and relatively rapid method for revealing cell morphologies to greatly facilitate the identification and characterization of retinal ganglion cells (RGCs) in rd1 retinas
The On ganglion cells that respond to light increments have axons terminating in the inner half of the inner plexiform layer (IPL), whereas the Off ganglion cells that respond to light decrements have axons which stratify in the outer half of the IPL [36]
Summary
The eye provides vision that relies on the integrity of cellular structures and functions of the retina. Like many other portions of the central nervous system (CNS), the retina is subject to a variety of inherited and acquired degenerative conditions [1,2]. The primary pathological event in many forms of retinal degeneration is the degeneration of photoreceptor cells, which serve to initiate the process of vision by converting light into neural signals. RP is a group of inherited human diseases characterized by progressive degeneration of photoreceptor cells and loss of photoreceptor function, eventually leading to functional blindness [3,4,5,6,7]. Understanding the pathophysiology of retinal degeneration and the accompanying changes in the cellular architecture of the retina is crucial for designing rational therapeutic interventions to rescue vision
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