gms | German Medical Science

The macula has evolved to offer detection of light over a very wide range of intensities and at exquisitely graded resolution whilst presumably optimising energy consumption as photoreceptors are intrinsically energy demanding and the system is ‘always on’. This is achieved through the intricate interplay of choroidal circulation, retinal pigment epithelium, photoreceptors and Muller cells.

It is well known that there are complex, co-independent interactions between choriocapillaris, retinal pigment epithelium and photoreceptors and in aging there are changes in each of these elements making it challenging to understand aging and age-related disorders such as AMD. These changes are likely to impact on the complex metabolic ecosystem operating in the outer retina eloquently described in recent years by Hurley and colleagues but direct measurements of metabolism at the back of the human eye currently presents significant challenges.

One approach to address these challenges is to use data from post-mortem tissue, ‘omics and the field of cell biology to construct computational models of the interplay between different cell types at the back of the eye. This approach can also be informed by the wealth of anatomical data available that describes how photoreceptor density and other parameters change with increasing eccentricity from the fovea.

It is interesting that models with rather simple ‘rules’ nevertheless display quite complex behaviour in relation to changing metabolite availability and some of the key patterns of metabolic fluxes determined experimentally are replicated in the models. The hope is that understanding of network control of metabolism may generate new approaches to therapy.