Assessment of neuroprotection in the retina with DARC

Prog Brain Res. 2008:173:437-50. doi: 10.1016/S0079-6123(08)01130-8.

Abstract

Currently, assessment of new drug efficacy in glaucoma relies on conventional perimetry to monitor visual field changes. However, visual field defects cannot be detected until 20-40% of retinal ganglion cells (RGCs), the key cells implicated in the development of irreversible blindness in glaucoma, have been lost. We have recently developed a new, noninvasive real-time imaging technology, which is named DARC (detection of apoptosing retinal cells), to visualize single RGC undergoing apoptosis, the earliest sign of glaucoma. Utilizing fluorescently labeled annexin 5 and confocal laser scanning ophthalmoscopy, DARC enables evaluation of treatment effectiveness by monitoring RGC apoptosis in the same living eye over time. Using DARC, we have assessed different neuroprotective therapies in glaucoma-related animal models and demonstrated DARC to be a useful tool in screening neuroprotective strategies. DARC will potentially provide a meaningful clinical end point that is based on the direct assessment of the RGC death process, not only being useful in assessing treatment efficacy, but also leading to the early identification of patients with glaucoma. Clinical trials of DARC in glaucoma patients are due to start in 2008.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Animals
  • Apoptosis / physiology
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Glaucoma / diagnosis
  • Glaucoma / drug therapy*
  • Glaucoma / pathology*
  • Glaucoma / physiopathology
  • Glutamic Acid / metabolism
  • Humans
  • Lasers
  • Neuroprotective Agents / therapeutic use*
  • Ophthalmoscopes
  • Ophthalmoscopy / methods*
  • Retinal Ganglion Cells / pathology*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / therapeutic use
  • Visual Field Tests / instrumentation
  • Visual Field Tests / methods
  • Visual Fields / physiology
  • Vitamins / therapeutic use

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Vitamins
  • Ubiquinone
  • Glutamic Acid
  • coenzyme Q10