Autophagy is an intracellular catabolic system, which enables cells to capture cytoplasmic components for degradation within lysosomes. Autophagy is involved in development, differentiation and tissue remodeling in various organisms, and is also implicated in certain diseases. Recent studies demonstrate that autophagy is necessary to maintain architecture and function of pancreatic beta cells. Altered autophagy is also involved in pancreatic beta cell death. Whether autophagy plays a protective or harmful role in diabetes is still not clear. In this review, we will summarize the current knowledge about the role of autophagy in pancreatic beta cell and diabetes.

Objectives. The complement system is a key component of innate immunity and has been implicated in the pathogenesis of diabetic retinopathy (DR). This study aimed at investigating whether polymorphisms of two genes in the complement pathway, complement factor H (CFH) and complement factor B (CFB), are associated with DR. Methods. 552 well-defined subjects with type 2 diabetes, consisting of 277 DR patients and 275 diabetic controls, were recruited. Four Tag-SNPs rs1048709, rs537160, rs4151657, and rs2072633 in CFB and rs800292 (I62V) in CFH were examined using TaqMan Genotyping Assays. Results. There were significant increases in the frequencies of A allele and AA genotype for rs1048709 in DR patients compared with diabetic controls (P corr = 0.035, OR = 1.42; P corr = 0.02, OR = 2.27, resp.): meanwhile, significant decreases in the frequencies of A allele and AA genotype for rs800292 were observed in DR patients compared with diabetic controls (P corr = 0.04, OR = 0.72; P corr = 0.015, OR = 0.51, resp.). Joint effect of these two loci was also identified. Moreover, rs800292/AA genotype was found to be related with delayed progression to DR. Conclusions. CFH-rs800292 and CFB-rs1048709 are associated with the presence of DR, which strengthens the concept that complement system plays an important role in the pathogenesis of DR.

Diabetic retinopathy (DR) has complex multifactorial pathogenesis. This study aimed to investigate the association of complement pathway genes with susceptibility to DR. Eight haplotype-tagging SNPs of SERPING1 and C5 were genotyped in 570 subjects with type 2 diabetes: 295 DR patients (138 nonproliferative DR [NPDR] and 157 proliferative DR [PDR]) and 275 diabetic controls. Among the six C5 SNPs, a marginal association was first detected between rs17611 and total DR patients (P = 0.009, OR = 0.53 for recessive model). In stratification analysis, a significant decrease in the frequencies of G allele and GG homozygosity for rs17611 was observed in PDR patients compared with diabetic controls (P corr = 0.032, OR = 0.65 and P corr = 0.016, OR = 0.37, resp.); it was linked with a disease progression. A haplotype AA defined by the major alleles of rs17611 and rs1548782 was significantly predisposed to PDR with increased risk of 1.54 (P corr = 0.023). Regarding other variants in C5 and SERPING1, none of the tagging SNPs had a significant association with DR and its subgroups (all P > 0.05). Our study revealed an association between DR and C5 polymorphisms with clinical significance, whereas SERPING1 is not a major genetic component of DR. Our data suggest a link of complement pathway with DR pathogenesis.

Emerging reports have revealed a potential association of paraoxonase (PON) gene polymorphisms with diabetic nephropathy (DN) and diabetic retinopathy (DR). However, the identification of susceptible genes and the quantification of associated risks are elusive owing to a lack of reproducibility. Therefore, a meta‑analysis was conducted in the present study to improve the understanding of the effect of PON1 and PON2 on DN and DR. A total of 10 articles, involving 2,877 patients and 3,246 controls met the inclusion criteria. Functional variants (n=4) were evaluated, including rs662 (p.Q192R) and rs854560 (p.L55M) in PON1; and rs7493 (p.S311C) and rs12026 (p.A148G) in PON2. Overall, PON1‑L55M was found to be significantly associated with DR in all the genetic models: allele [odds ratio (OR)=2.42; 95% confidence interval (CI), 1.91‑3.07]; dominant (OR=5.76; 95% CI, 3.14‑10.55), homozygote (OR=10.53; 95% CI, 5.59‑19.86), heterozygote (OR=3.62; 95% CI, 1.94‑6.74), and recessive (OR=3.56; 95% CI, 2.61‑4.86), with no evidence of between‑study heterogeneity. However, such associations were not detected in DN and the other three polymorphisms did not show any associations with DN or DR. The current meta‑analysis highlighted results for the risk of association of PON1‑55L with DR. The results also indicated that PON2 gene polymorphisms, as well as PON1‑Q192R, may not confer major genetic risk to DN or DR. Additional studies are required to enrich the understanding of PON genes, particularly for its functional role in DR.