Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries, including glaucoma, diabetic retinopathy, traumatic optic neuropathy and optic neuritis, etc. . The current clinical treatment is not very effective. We investigated indirubin, one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill, in the present study for its role in retinal neurodegeneration. Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro. . Moreover, indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo. . Furthermore, indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro. . In addition, indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress. Mechanically, indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling. In conclusion, indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury. The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells (ECs). They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier (BRB)/blood-brain barrier (BBB). The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This potential enables pericytes to be a potential biomarker for the diagnosis and a target for treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

Congenital aniridia is a rare autosomal dominant congenital ocular disorder. Genetic studies suggest that heterozygous mutations in the developmental regulator PAX6 gene or the related regulatory regions leading to haploinsufficiency are the main cause of congenital aniridia. In this study, the clinical characteristics and pathogenic mutation of a four-generation Chinese family with congenital aniridia were investigated. All members recruited in this study underwent comprehensive ophthalmic examinations. Targeted gene capture sequencing and Sanger sequencing were performed to screen and confirm the candidate pathogenicity gene and its mutation. A multiple alignment of homologous sequences covering the identified mutation from different species was investigated, and the mutant protein structure was predicted using Swiss-Model. Additionally, the prediction of pathogenicity was analyzed using the ACMG Guidelines. Thirteen patients in this pedigree were diagnosed with congenital aniridia. A novel heterozygous frameshift mutation (c.391_398dupATACCAAG, p.Ser133Argfs*8) in exon 7 of the PAX6 gene was identified in all affected individuals in the family. This study demonstrates that this frameshift mutation of the PAX6 gene might be the causative genetic defect of congenital aniridia in this family. This mutation is predicted to cause the premature truncation of the PAX6 protein, leading to the functional haploinsufficiency of PAX6, which may be the major molecular mechanism underlying the aniridia phenotype. To the best of our knowledge, this is the first report of a novel pathogenic PAX6 gene variant c.391_398dupATACCAAG(p.Ser133Argfs*8) identified in a Chinese family with congenital aniridia.