Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration

Mol Vis. 2011:17:1716-33. Epub 2011 Jun 25.

Abstract

Purpose: To analyze the damage produced by light in mydriatic and miotic albino retinas under two different sources of light.

Methods: Albino Sprague Dawley female rats were exposed to 3,000 lx during 48 h under two different light sources: linear and circular bulbs. Before exposure, their left pupils were dilated. Before and at different times after light exposure (ALE), electroretinographic signals were recorded. One week before processing, retinal ganglion cells (RGCs) were traced by applying fluorogold on the superior colliculi. Just before processing, some animals were intravenously injected with horseradish peroxidase to analyze retinal vascular leakage. At different times ALE, animals were sacrificed and their retinas dissected as whole mounts or cross-sections. Cross-sections were used to study the retinal degeneration and to detect apoptotic nuclei by the transferase dUTP nick end labeling (TUNEL) technique. Whole mounts were used to analyze vascular leakage; investigate the nerve fiber layer, identified by immunodetection of neurofilaments; and quantify the whole population of RGCs identified by fluorogold tracing and Brn3a immunodetection. With the quantitative data, detailed isodensity maps were generated to study the spatial loss of RGCs.

Results: Phototoxicity causes an immediate and permanent abolishment of the electroretinographic response. Early ALE, photoreceptors degenerate by apoptosis and this death is more severe in mydriatic conditions and under circular bulbs. Photoreceptor loss starts in an arciform dorsomedial retinal area, but at 3 months ALE has spread to the whole retina and there are no differences related to either pupil dilation or light source. Three months ALE, RGC axons show distorted trajectories and abnormal expression of neurofilaments. Six months or more ALE, there is significant death of RGCs caused by axonal strangulation by displaced inner retinal vessels. Topography of the surviving RGCs shows that their loss is not uniform throughout the retina.

Conclusions: Light damage to photoreceptors depends on pupil dilation and light source, but affects all retinal layers with time. These deteriorative events are also observed in light-induced and inherited retinal degenerations in pigmented animals, but occur differently. Thus, the role of ocular pigmentation and the etiology of photoreceptor degeneration on retinal remodelling deserve further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism
  • Animals
  • Apoptosis / radiation effects
  • Axons / radiation effects*
  • Dilatation / methods
  • Electroretinography
  • Female
  • Immunohistochemistry
  • Light / adverse effects
  • Microtomy
  • Photoreceptor Cells* / cytology
  • Photoreceptor Cells* / metabolism
  • Photoreceptor Cells* / radiation effects
  • Pigmentation
  • Pupil / radiation effects
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Degeneration*
  • Retinal Ganglion Cells* / cytology
  • Retinal Ganglion Cells* / metabolism
  • Retinal Ganglion Cells* / radiation effects
  • Retinal Vessels / radiation effects