Background: To investigate the role of microglia polarization in the pathogenesis of diabetic retinopathy, and study the mechanism of ALKBH5-mediated m⁶A modification of A20 of retinal microglia polarization.Methods: Diabetics rats were constructed and the M1/M2 polarization of retinal microglia was determined using immunofluorescence, flow cytometry, and quantitative real-time PCR (qRT-PCR). Glucose at different concentrations was added to treat the microglia, and the polarization rate was detected. RNA sequencing was performed to identify the differentially expressed gene in glucose treated microglia, and A20 expression was confirmed by qRT-PCR and western blotting. Lentiviruses encoding shRNA for A20 or overexpressing A20 were constructed to clarify the role of A20 in microglia polarization in vitro and vivo. N⁶-methyladenosine (m⁶A) modification level and degradation rate of A20 were determined and m⁶A related proteins were detected.Results: Diabetics rats showed a higher M1 polarization rate but lower M2 polarization rate of retinal microglia. With the increase of glucose concentration, microglia tend to polarize into M1 inflammatory type rather than M2 anti-inflammatory type. Shown by RNA sequencing, glucose treated microglia showed a differentially expressed gene profile, which was enriched in kinds of inflammatory categories and pathways. A20 expression was lower in microglia with glucose treatment, which was demonstrated to negatively regulate the M1 polarization. Moreover, intraocular injection of A20-overexpression lentiviruses (OE-A20) rectified the enhanced M1 retinal microglia polarization of diabetes rats. The higher m⁶A modification level and faster degradation rate of A20 was observed in glucose treated microglia, which was mediated by m⁶A demethylase ALKBH5.Conclusion: Lower expression A20 resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m⁶A modification. This study may provide new perspectives on not only the pathogenesis but also the diagnosis and treatment for diabetic retinopathy.

Background: The study aimed to investigate the difference in refractive status and ocular parameters between ptotic and fellow eyes in patients with unilateral congenital ptosis. Methods: Thirty patients (53% males, age 22.00 ± 11.41 years) with unilateral congenital ptosis diagnosed and treated at the First Affiliated Hospital of Sun-yat Sen University were enrolled and underwent detailed refractive examinations from March 2019 to February 2022. Ocular biometric measurements were performed by an IOL Master 700 biometer. The differences in refractive error characteristics, best-corrected visual acuity (BCVA), and ocular parameters including axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), lens thickness (LT), and keratometry values between ptotic and fellow eyes were analysed. Results: A lower BCVA (logMAR, median (IQR), 0.00 (− 0.13,0.00), P = 0.009) and a higher incidence of amblyopia (n (%), 7(23%), P = 0.016) were observed in ptotic eyes. The CCT of ptotic eyes was greater than that of fellow eyes (mean ± SD, 539.83 ± 26.73 μm, P < 0.001). The keratometry values at the flat axis (K1) and mean corneal power (Km) were smaller in ptotic eyes (mean ± SD, 42.11 ± 1.49 D, 42.68 ± 1.52 D, respectively, both P = 0.001). There was no significant difference in AL between ptotic and fellow eyes. Conclusions: Congenital ptosis influences ocular parameters, mainly causing a thicker and flatter cornea. Patients with unilateral congenital ptosis might have lower BCVA in the ptotic eyes.

BackgroundThe study aimed to investigate the difference of refractive status and ocular parameters between ptotic and fellow eyes in patients with unilateral congenital ptosis.Methods25 patients (52% males, age 22.04±10.96) with unilateral congenital ptosis diagnosed and treated at the First Affiliated Hospital of Sun-yet Sen University were enrolled and underwent detailed refractive examination from March 2019 to November 2021. Ocular biometric measurements were performed by IOL Master 700 biometer. The difference of refractive error characteristics, best-corrected acuity (BCVA), as well as ocular parameters including axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), lens thickness (LT), and keratometry values between ptotic and fellow eyes were analyzed.ResultsLower BCVA (p=0.01) and higher incidence of amblyopia (p=0.018) were observed in ptotic eyes. Among patients with amblyopia, the presence (p=0.038) and magnitude (p=0.044) of astigmatism were higher in ptotic eyes. The CCT of ptotic eyes was thicker than that of fellow eyes (p＜0.001). The keratometry values at the flat axis (K1), and mean corneal power (Km) were smaller (both p＜0.001). There was no statistical difference of AL between ptotic and fellow eyes.ConclusionsCongenital ptosis influenced ocular parameters, mainly causing a thicker and flatter cornea. Patients with unilateral congenital ptosis might have lower BCVA in ptotic eyes, while higher amblyogenic astigmatism was observed.