Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis

Abstract

We review proposed models and psychophysical and electrophysiological tests performed in many studies for early agerelated maculopathy (ARM). We suggest that ischaemia is the trigger for impaired retinal pigment epithelium function causing imbalance of secretion of vascular growth factors, reduced disc degradation capability and reduced metabolic activity and possible inflammatory response. This results in increased deposition of cell debris, such as drusen and thickens Bruch's membrane causing even more ischaemia of the overlying neurosensory retina. The photoreceptors are more resistant to ischaemia given their proximity to the choroid. Furthermore, being 'upstream' from the inner retinal layers, they act as an oxygen sink depriving retinal layers further from the choroid. Postreceptoral cell layers and especially parts of the inner nuclear layer that are located in the watershed zone between two sources of blood supply are preferentially vulnerable to ischaemia. Based on psychophysical and electrophysiological findings we propose that most of the function impairment in early ARM starts postreceptorally.

The electroretinogram: a useful tool for evaluating age-related macular disease?

“…Hypoxia has been experimentally induced in younger and older healthy eyes resulting in a reduction in central and peripheral neuroretinal function indicated by reduced mfERG response densities [41,65,66]. This supports the hypothesis that post-receptoral vulnerability occurs during reduced oxygenation and ischaemia [52,67].…”

Macular Ganglion Cell Complex and Retinal Nerve Fiber Layer Comparison in Different Stages of Age-Related Macular Degeneration

“…Alternatively, inner retinal ganglion cells may perish from progressive hypoperfusion secondary to macular aging. Chronic failure of choroidal vasculature might be responsible for postreceptoral damage in all AMD stages, a theory known as the ischaemia postreceptoral hypothesis 21 .…”

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…Evidence suggests that the macular choroid is particularly vulnerable to ischaemia due to the number of watershed zones that meet there (Hayreh 1974(Hayreh , 1983Kornzweig 1977). Feigl et al (2007a) proposed that post-receptoral neurons which are located in the watershed zone may be more vulnerable to ischemia, whereas the photoreceptors may be more resistant to ischemic insult due to their proximity to metabolic reserves in the RPE and the choriocapillaris (Cringle, Yu, Yu & Su 2002). This hypothesis is supported by histopathological findings showing that when the RPE degenerates, the post-receptoral outer plexiform and inner nuclear layers are first affected (Sarks et al 1988).…”

“…Arden et al (2005) proposed that ischaemia in AMD is driven by the high oxygen demand of the rods that cannot be met due to altered RPE function. Whether RPE dysfunction is a consequence of reduced choroidal blood flow in AMD remains to be determined (Feigl et al 2007a). A functional RPE is required to maintain retinal health and synthesize 11-cis-retinal through the retinoid cycle (Baehr, Wu, Bird & Palczewski 2003).…”