Abstract
Purpose :
Macular degeneration is one of the prime causes of blindness, presenting irreversible photoreceptor cell degeneration. Inflammation is the underlying mechanism of photoreceptor degeneration in the retina, thus control mechanism of the retinal inflammation needs to be elucidated. Zap-70 is a well-known inflammatory modulator expressed in the T-lymphocyte. However, the expression pattern and importance of Zap-70 in retinal degeneration are not understood. In this study, we demonstrated the expression of the Zap-70 in the blue-LED induced photoreceptor mice model, and we showed exacerbation of the inflammation in the retina by activating the Zap-70 using SKG mouse.
Methods :
To explore photoreceptor cell loss, we used blue-LED induced photoreceptor degeneration model. SKG mice with active Zap-70 mutations and wild-type Balb/c mice were used to study photoreceptor degeneration. The mice were exposed to blue-LED light, and their visual function was examined using an electroretinogram (ERG) and photoreceptor cell death was determined using the TUNEL assay. The qPCR was used to detect mRNA signals for multiple cytokines, including Il1, Il6, Il17, Il10, and TNF, while Western blot and immunohistochemistry were used to detect ZAP-70 expression in the retina.
Results :
Visual function was significantly impaired in blue LED light-exposed mouse groups and had an adverse impact on mice with Zap-70 mutations. In addition, photoreceptor cell death was more prominent in the SKG mice than wild-type mice. SKG mice demonstrated significantly greater levels of inflammatory cytokines in the blue-LED exposed groups than wild-type mice. And Zap-70 expression was detected in the active microglial cells, which were located in the outer nuclear layer of the injured retina.
Conclusions :
We identified that Zap-70 is expressed in the microglial cells in the blue-LED induced retinal degeneration (RD) model, and it increased inflammatory activity in the retina, which upregulated several inflammatory cytokines and exacerbated photoreceptor cell death. We first described that Zap-70 is not only an immune modulator of the T-lymphocyte but could also act in the retina to intensify pro-inflammatory processes. Clinically we offered significant information because Zap-70 is a major regulator in autoimmune disease, thus it suggests that individuals experiencing inflammatory disease could be more vulnerable to photoreceptor impairment.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.