Adeno-associated virus (AAV) vector-mediated delivery of inhibitors of blood-retinal barrier breakdown (BRBB) offers promise for the treatment of diabetic macular edema. Here, we demonstrated a reversal of blood-retinal barrier pathology mediated by AAV type 2 (AAV2) vectors encoding vasoinhibin or soluble VEGF receptor 1 (sFlt-1) when administered intravitreally to diabetic rats. Efficacy and safety of the AAV2 vasoinhibin vector were tested by monitoring its effect on diabetes-induced changes in the retinal vascular bed and thickness, and in the electroretinogram (ERG). Also, the transduction of AAV2 vectors and expression of AAV2 receptors and co-receptors were compared between the diabetic and the non-diabetic rat retinas. AAV2 vasoinhibin or AAV2 sFlt-1 vectors were injected intravitreally before or after enhanced BRBB due to diabetes induced by streptozotocin. The BRBB was examined by the Evans blue method, the vascular bed by fluorescein angiography, expression of the AAV2 EGFP reporter vector by confocal microscopy, and the AAV2 genome, expression of transgenes, receptors, and co-receptors by quantitative PCR. AAV2 vasoinhibin and sFlt-1 vectors inhibited the diabetes-mediated increase in BRBB when injected after, but not before, diabetes was induced. The AAV2 vasoinhibin vector decreased retinal microvascular abnormalities and the diabetes-induced reduction of the B-wave of the ERG, but it had no effect in non-diabetic controls. Also, retinal thickness was not altered by diabetes or by the AAV2 vasoinhibin vector. The AAV2 genome, vasoinhibin and sFlt-1 transgenes, and EGFP levels were higher in the retinas from diabetic rats and were associated with an elevated expression of AAV2 receptors (syndecan, glypican, and perlecan) and co-receptors (fibroblast growth factor receptor 1, αvβ5 integrin, and hepatocyte growth factor receptor). We conclude that retinal transduction and efficacy of AAV2 vectors are enhanced in diabetes, possibly due to their elevated cell entry. AAV2 vectors encoding vasoinhibin and sFlt-1 may be desirable gene therapeutics to target diabetic retinopathy and macular edema.

High serum prolactin and vasoinhibin levels predict and may impact ROP progression.

The hormone prolactin (PRL) is emerging as an important regulator of ocular blood vessels. PRL is pro-angiogenic and acquires anti-angiogenic properties after undergoing proteolytic cleavage to the PRL fragment, vasoinhibin. The vascularisation of the rodent retina develops after birth when it rapidly expands until completion at the end of the first postnatal week. Exposure of newborn mice to high oxygen levels lowers

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Purpose To discuss diagnosis and management in the case of a patient presenting with bilateral ischemic retinal vasculopathy associated with a previously undiagnosed IgA nephropathy. Case report In 2021, a 35-year-old male presented with a sudden onset asymmetric bilateral (OU) visual loss. Best-corrected visual acuity (BCVA) was 20/200 OD, and no light perception (NLP) OS with an associated relative afferent pupillary defect (RAPD). Slit-lamp examination (SLE) confirmed normal anterior segment anatomy OU. Indirect ophthalmoscopy and subsequent fluorescein angiography (FA) confirmed the presence of bilateral arterial attenuation, telangiectatic lesions, associated perivascular sheathing, and capillary leakage. Spectral domain optical coherence tomography (OCT) showed multiple areas of thinning of the inner retina. This constellation of diagnostic findings was highly suggestive of a bilateral ischemic retinal vasculopathy with an inflammatory vasculitis. Based on a high index of suspicion for a systemic etiology, nephrology was consulted, and a diagnosis of IgA nephropathy was confirmed by renal biopsy. Systemic immunomodulatory therapy was initiated. Conclusion Although it is among the most commonly occurring forms of glomerulonephritis leading to renal failure, IgA nephropathy rarely presents with a bilateral retinal vasculopathy. Schölein – Henoch purpura, the other primary disease associated with glomerular IgA deposition, may be indistinguishable from primary IgA nephropathy. A comprehensive retinal examination with multimodal functional and structural ophthalmic diagnostic testing in conjunction with renal biopsy was needed to confirm the diagnosis. It is critical to include primary renal pathology when formulating a differential diagnosis for cases of bilateral retinal vasculitis, particularly in young otherwise healthy patients.