<p>The cGAS/STING pathway: a sensor of senescence-associated DNA damage and trigger of inflammation in early age-related macular degeneration</p>

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly. Considering the relatively limited effect of therapy on early AMD, it is important to focus on the pathogenesis of AMD, especially early AMD. Ageing is one of the strongest risk factors for AMD, and analysis of the impact of ageing on AMD development is valuable. Among all the ageing hallmarks, increased DNA damage accumulation is regarded as the beginning of cellular senescence and is related to abnormal expression of inflammatory cytokines, which is called the senescence-associated secretory phenotype (SASP). The exact pathway for DNA damage that triggers senescence-associated hallmarks is poorly understood. Recently, mounting evidence has shown that the cGAS/STING pathway is an important DNA sensor related to proinflammatory factor secretion and is associated with another hallmark of ageing, SASP. Thus, we hypothesized that the cGAS/STING pathway is a vital signalling pathway for early AMD development and that inhibition of STING might be a potential therapeutic strategy for AMD cases.

Comparative efficacy and safety of anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: systematic review and Bayesian network meta-analysis

“…CRT change may also implicate the morphological disruption and dysfunction of the inner or outer blood-retinal barrier during the development of disease. 54 – 58 …”

Future perspective: high-throughput construction of new ultrasensitive cytokine and virion liquid chips for high-throughput screening (HTS) of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases

“…The newly constructed cytokine and virion liquid sensors have significant value for clinical diagnosis and treatment of infectious and inflammatory diseases (Figs. 5 and 6) [27,36,42]. Engineering Research Center of Ta r g e t e d a n d I n n o v a t i v e Therapeutics.…”

“…Both the membrane protein receptors (Fig. 6a) and the transcription factor NF-kB and NLRP2 proteins can be designed as drugs for blocking the membrane protein interactions or blocking the protein aggregation and DNA binding properties to suppress inflammation in the human body [36,42].…”

The Emerging Role of Senescence in Ocular Disease

“…Recent mechanistic studies show that stimulated by cytosolic DNA, active cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway triggers inflammation and plays a role in the development of senescence [228]. Based on these findings, it was hypothesized that blocking STING pathway could be a potential therapeutic strategy to prevent senescenceassociated human diseases [229]. All the preclinical animal studies in different disease models with an array of senolytic agents provide confidence in bringing senolytic agents into clinical trials.…”