Macular Degeneration (MD) affects central vision. It is most commonly observed in people over the age of 60. It is much more common in whites than in blacks or hispanics. Severity is divided into early, intermediate, and late types. The late type is additionally divided into “dry” and “wet” forms, with the dry form making up 90% of cases. Those with the dry form show accumulation of drusen in the macula that leads to central vision vision loss.
Drusen, from the German word for node or geode, are tiny yellow or white accumulations of extracellular material that build up in the eye. The presence of a few small drusen is normal with advancing age, and most people over 40 have some drusen. However, the presence of larger and more numerous drusen in the macula is a common early sign of age-related macular degeneration. Whether drusen promotes MD or is symptomatic of an underlying process that causes both drusen and MD is not known, but they it is an indicator of increased risk of the complications of MD. For a detailed discussion of the disorder go here.
Dalvi and colleagues studied the accumulation of drusen in pluripotent stem cells from patients with age-related MD. The abstract from their paper is below. I have edited out the numerous abbreviations which render the summary almost unintelligible. Even with these changes the text is still a challenge. I added a few words to improve clarity, but it remains a slog.
Age-related macular degeneration and related macular dystrophies primarily affect the retinal pigment epithelium in the eye. A hallmark of Age-related MD/macular dystrophies that drives later-stage pathologies is drusen. Drusen are sub-retinal epithelium lipid-protein-rich extracellular deposits, but how drusen forms and accumulates is not known. We utilized human induced pluripotent stem cell-derived retinal pigment epithelium from patients with Age-related MD and three distinct macular dystrophies to demonstrate that reduced activity of retinal pigment epithelium-secreted matrix metalloproteinase 2 contributes to drusen in multiple maculopathies in a genotype-agnostic manner by instigating sterile inflammation and impaired lipid homeostasis via a damage-associated molecular pattern molecule-mediated activation of the receptor for advanced glycation end-products and increased secretory phospholipase 2-IIA ) levels. Therapeutically, retinal pigment epithelium-specific matrix metalloproteinase 2 supplementation, receptor for advanced glycation end-products-antagonistic peptide, and a small molecule inhibitor of secretory phospholipase 2-IIA ameliorated drusen accumulation in Age-related MD/macular dystrophies induced pluripotent stem cell-retinal pigment epithelium. Ultimately, this study defines a causal role of the matrix metalloproteinase 2-damage-associated molecular pattern molecule-receptor for advanced glycation end-products-secretory phospholipase 2-IIA-IIA axis in AMD/macular dystrophies.
What the study shows is in stem cells in a laboratory setting that increasing matrix metalloproteinase 2 levels reduced drusen accumulation. The authors hope that the development of therapies designed to do the same in patients with MD will prove beneficial. As we don’t know whether drusen formation is a cause or result of MD it will be a long time before we learn if therapies intended to reduce drusen accumulation will ameliorate Age-related MD. Still any new approach to the treatment of MD a major cause of blindness is welcome and deserves further research.