Retinal ganglion cells are resistant to photoreceptor loss in retinal degeneration

PLoS One. 2013 Jun 28;8(6):e68084. doi: 10.1371/journal.pone.0068084. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dependovirus / metabolism
  • Disease Models, Animal
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Photoreceptor Cells / metabolism
  • Photoreceptor Cells / physiology*
  • Retina / metabolism
  • Retina / physiopathology
  • Retinal Degeneration / physiopathology*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / physiology*
  • Retinitis Pigmentosa / physiopathology

Substances

  • enhanced green fluorescent protein
  • Green Fluorescent Proteins

Grants and funding

This work was supported by The University of Hong Kong Seed Funding Program for Basic Research and General Research Fund from the Hong Kong Research Grants Council (772810). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.