Dynamic Expression of HDAC3 in db/db Mouse RGCs and Its Relationship with Apoptosis and Autophagy

Abstract

Background. Diabetic retinopathy (DR) is a severe complication of diabetes mellitus. DR is considered as a neurovascular disease. Retinal ganglion cell (RGC) loss plays an important role in the vision function disorder of diabetic patients. Histone deacetylase3 (HDAC3) is closely related to injury repair and nerve regeneration. The correlation between HDAC3 and retinal ganglion cells in diabetic retinopathy is still unclear yet. Methods. To investigate the chronological sequence of the abnormalities of retinal ganglion cells in diabetic retinopathy, we choose 15 male db/db mice (aged 8 weeks, 12 weeks, 16 weeks, 18 weeks, and 25 weeks; each group had 3 mice) as diabetic groups and 3 male db/m mice (aged 8 weeks) as the control group. In this study, we examined the morphological and immunohistochemical changes of HDAC3, Caspase3, and LC3B in a sequential manner by characterizing the process of retinal ganglion cell variation. Results. Blood glucose levels and body weights of db/db mice were significantly higher than that of the control group, P < 0:01. Compared with the control group, the number of retinal ganglion cells decreased with the duration of disease increasing. HDAC3 expression gradually increased in RGCs of db/db mice. Caspase3 expression gradually accelerated in RGCs of db/db mice. LC3B expression dynamically changed in RGCs of db/db mice. HDAC3 was positively correlated with Caspase3 expression (r = 0:7424), P < 0:01. HDAC3 was positively correlated with LC3B expression (r = 0:7336), P < 0:01. Discussion. We clarified the dynamic expression changes of HDAC3, Caspase3, and LC3B in retinal ganglion cells of db/db mice. Our results suggest the HDAC3 expression has a positive correlation with apoptosis and autophagy.

Therapeutic potential of curcumin in diabetic retinopathy (Review)

“…In the high glucose state, the expression of MMP-2 increases, while the expression of heat shock protein 60 and connexin 43 decreases, leading to mitochondrial membrane degradation, increased apoptosis, and more severe DR ( 83 , 84 ). On the basis of in vitro and in vivo experiments, researchers have demonstrated that in retinal ganglion cells of mice with STZ-induced diabetes, the expression of caspase-3 gradually increases ( 85 ). In addition, as previously demonstrated, the apoptosis of adult retinal pigment epithelial cells (ARPE-19 cells) that were cultured under high glucose conditions also significantly increased ( 86 ).…”

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

“…The modulation of autophagy in diabetic models may vary depending on the progression of the disease and therefore on the time points analyzed. In RGCs of C57BL/KsJ-db/db mouse, a rodent model of spontaneous diabetes, Fu and co-workers (2020) observed a fluctuating modulation of LC3-II protein levels depending on the age of diabetic mice without identifying a clear trend (Fu et al, 2020). In db/db mice Luo and colleagues reported a downregulation of pro-autophagy proteins like LC3-II, Beclin-1 and Atg5 and a significant upregulation of p62 (Luo et al, 2021).…”

Downregulated HDAC3 or up-regulated microRNA-296-5p alleviates diabetic retinopathy in a mouse model

“…The injection was conducted in both eyes and repeated twice a week until nine injections were completed. Mice without any treatment were set in the control group [ 10 ].…”

“…A previous study has contended that HDAC3, as a new mechanism for kidney injury, provides a potential therapeutic target for type 2 diabetes [ 9 ]. Also, HDAC3 is dynamically expressed in retinal ganglion cells in DR, which is associated with cellular apoptosis and autophagy [ 10 ]. MicroRNAs (miRNAs) are a series of endogenous ncRNAs that suppress downstream target genes expression via post-transcriptional modulation [ 11 ].…”