Photoreceptor degeneration in aging and age-related maculopathy

Chapter

Abstract

  • In summary, anatomical and functional studies have converged to demonstrate that photoreceptor degeneration and loss occurs before disease in the RPE/Bruchs membrane complex progresses to late ARM. Furthermore, macular rods are affected earlier and more severely than cones in aging and ARM. These findings are significant for both clinical and basic research. In many patients tests of rod function may permit detection of ARM at earlier stages than do standard tests of cone function such as visual acuity. The preferential vulnerability of rods in aging and ARM is a phenomenon which should be accounted for by mechanistic theories. These findings provide a standard against which the relevance of emerging animal models (Mata et al. 2001; Rakoczy et al. 2002;Weber et al. 2002) and other potentially pathogenic phenomena in the macula should be assessed. Since rods secrete factors that enhance cone survival (Mohand-Said et al. 1998), early interventions that target rod photoreceptors may have an indirect salutatory effect on cones as well. The link between photoreceptor dysfunction, assessed by vision function studies, and risk for neovascularization in Bruchs membrane, alluded to at the beginning of this review, is most plausibly attributable to the common cause of poor RPE health, long postulated as central to ARM pathogenesis (Hogan 1972). Because the RPE is polarized, problems pertaining to the resupply of photoreceptors on the apical aspect of the RPE (leading to photoreceptor death) should be conceptually separated from problems pertaining to waste removal on the basal aspect of the RPE (leading to Bruchs membrane damage and neovascularization), at least for the purposes of designing mechanistic experiments. These processes are governed by different proteins and pathways at the cellular level and will be reflected by different risk factors and genetic predispositions at the population level. Rigorous test of a nutrient deficiency hypothesis of ARM-associated photoreceptor death, awaits more information about normal nutrient delivery mechanisms across the RPE/ Bruchs membrane complex, intraretinal contributions to photoreceptor nutrition, changes in these mechanisms with age and pathology, and differential effects on rods and cones.
  • Digital Object Identifier (doi)

    International Standard Book Number (isbn) 10

  • 3540200584
  • International Standard Book Number (isbn) 13

  • 9783540200581
  • Start Page

  • 45
  • End Page

  • 62