“Wet” age-related C (AMD) is likely one of the most common causes of irreversible vision loss in the elderly, and it occurs when ordinary and leaky blood vessels form in the retina, in part because of inflammation. New research reveals insights into potential drivers of the disease — which currently has no cure — which may be targeted through prevention or remedy strategies.
The findings of the study by investigators at Massachusetts General Hospital (MGH) are published in eLife.
Two inflammatory pathways involving complement (which is an immune system component) and a protein complex called the inflammasome (which, as its name suggests, triggers inflammation) promote the formation of ordinary blood vessels that are hallmarks of wet AMD, but it’s unclear how these pathways are activated. Preceding studies propose that the inflammasome could also be activated by a protein called NLRP3, chiefly in the retinal pigment epithelium of the eye (a cell layer that separates the vascular layer of the eye from the retina).
To enquire further, researchers conducted experiments in a mouse mannequin of wet AMD. The team showed that inflammasome activation by NLRP3 occurs chiefly in cells called macrophages and microglia, but not in the retinal pigment epithelium. The scientists also discovered that proteins other than NLRP3 may end up in inflammasome activation and worsening of wet AMD.
“Which means quite than targeting only NLRP3 in wet AMD, it can be really helpful to block fundamental proteins of the inflammasome instead that are required for its activation, independently of if NLRP3 or other proteins initiate inflammasome activation,” explains senior writer Alexander G. Marneros, MD, PhD, a principal investigator at MGH’s Cutaneous Biology Research Center and an associate professor of dermatology at Harvard Medical School. “Our findings supply guidance on how to block inflammasomes in wet AMD.”
Marneros paper money that preceding studies conducted in cells propose that complement activation can in turn lead to inflammasome activation, but this study in mice found that this activation occurs in large part independently from complement-mediated inflammation. “Our study in a mouse mannequin defines the cell types that contribute to inflammasome-mediated inflammation in wet AMD and uncovers the particular roles and contributions of NLRP3 inflammasomes, non-NLRP3-inflammasomes, and complement for the manifestation of wet AMD,” he says.
Along with providing new insights into how inflammation is regulated in wet AMD, the study also suggests that novel therapies that block inflammasome-mediated inflammation could be improved when combined with treatments that inhibit complement-mediated inflammation. “A combined therapeutic approach that blocks both these inflammatory pathways is likely going to have synergistic effects in lessening the symptoms of wet AMD. Thus, our findings in this mouse mannequin may have important clinical relevance for novel therapies for this common blinding disease,” says Marneros.
(This story has been published from a wire agency feed without modifications to the text.)
Follow more stories on Facebook and Twitter[ad_2]