A Fairy Chemical Suppresses Retinal Angiogenesis as a HIF Inhibitor.

Neovascular retinal degeneration is a leading cause of blindness in advanced countries. Anti-vascular endothelial growth factor (VEGF) drugs have been used for neovascular retinal diseases; however, anti-VEGF drugs may cause the development of chorioretinal atrophy in chronic therapy as they affect the physiological amount of VEGF needed for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcription factor inducing VEGF expression under hypoxic and other stress conditions. Previously, we demonstrated that HIF was involved with pathological retinal angiogenesis in murine models of oxygen-induced retinopathy (OIR), and pharmacological HIF inhibition prevented retinal neovascularization by reducing an ectopic amount of VEGF. Along with this, we attempted to find novel effective HIF inhibitors. Compounds originally isolated from mushroom-forming fungi were screened for prospective HIF inhibitors utilizing cell lines of 3T3, ARPE-19 and 661W. A murine OIR model was used to examine the anti-angiogenic effects of the compounds. As a result, 2-azahypoxanthine (AHX) showed an inhibitory effect on HIF activation and suppressed Vegf mRNA upregulation under CoCl2-induced pseudo-hypoxic conditions. Oral administration of AHX significantly suppressed retinal neovascular tufts in the OIR model. These data suggest that AHX could be a promising anti-angiogenic agent in retinal neovascularization by inhibiting HIF activation.

Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury.

γδ T cells located near the epithelial barrier are integral components of local inflammatory and innate immune responses. We have previously reported the presence of choroidal γδ T cells in a model of chronic degeneration of the retinal pigment epithelium (RPE). The goals of the current study were to further define the functions of choroidal γδ T cells and to explore the underlying mechanisms of their action. Our data demonstrate that choroidal γδ T cells are activated by RPE injury in response to NaIO3 treatment, and that they express genes that encode immunosuppressive cytokines, such as IL-4 and IL-10. γδ-T-cell-deficient mice developed profound RPE and retinal damage at doses that caused minimal effects in wild-type mice, and adoptive transfer of γδ T cells prevented sensitization. Intravitreal injection of IL-4 and IL-10 ameliorated RPE toxicity that was induced by NaIO3Ex vivo coculture of γδ T cells with RPE explants activated the production of anti-inflammatory cytokines via an aryl hydrocarbon receptor (AhR)-dependent mechanism. AhR deficiency abolished the protective effects of γδ T cells after adoptive transfer. Collectively, these findings define important roles for choroid γδ T cells in maintaining tissue homeostasis in the outer retina.-Zhao, Z., Liang, Y., Liu, Y., Xu, P., Flamme-Wiese, M. J., Sun, D., Sun, J., Mullins, R. F., Chen, Y., Cai, J. Choroidal γδ T cells in protection against retinal pigment epithelium and retinal injury.

[Two cases of phototherapeutic keratectomy treatment of the recurrent corneal erosion caused by alkali burn]. / Behandlung zweier Patienten mit einer zeitgleichen, arbeitsbedingten Augenlaugenverätzung und konsekutiver rezidivierender Erosio corneae mittels phototherapeutischer Keratektomie.

BACKGROUND: Four eyes of two patients were injured simultaneously by industrial alkali while working. One eye of both patients healed without later consequences. PATIENTS AND METHODS: Two eyes were treated with phototherapeutic keratectomy (PTK) because of recurrent corneal erosion syndrome caused by alkali burn. RESULTS: In both cases reepithelisation of the cornea was completed by the end of the 1st postoperative week, the injured persons were able to work again. No recurrence was experienced in the next 6 months of follow-up. CONCLUSION: With these cases the authors would like to draw attention to the possible complications, as well as the importance of careful balancing and adequate management.

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review.

PURPOSE: To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma. METHODS: PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans. RESULTS: Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments. CONCLUSIONS: Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

Spectral-domain optical coherence tomography as a screening technique for chloroquine and hydroxychloroquine retinal toxicity.

BACKGROUND AND OBJECTIVE: To determine the effectiveness of spectral-domain optical coherence tomography (SD-OCT) as a screening tool for the evaluation of chloroquine or hydroxychloroquine retinal toxicity. PATIENTS AND METHODS: This is a prospective, case-control study. Subject eyes were divided into four groups (group I = eyes with bull's eye maculopathy, group II = eyes with early changes of toxicity, group III = eyes with exposure but no signs of toxicity, and group IV = eyes of age-matched controls). Retinal thickness was measured via SD-OCT 0.5 and 1.0 mm from the foveal center. RESULTS: Mean retinal thickness 1.0 mm from the fovea in group I eyes was significantly thinner when compared to group IV. Eyes in group II also showed retinal thinning 1.0 mm from the foveal center when compared to both groups III and IV. Mean retinal thickness 0.5 mm from the foveal center did not differ significantly between any groups. CONCLUSION: Significant retinal thinning occurred 1.0 mm, but not 0.5 mm, from the foveal center in patients with early and late chloroquine or hydroxychloroquine toxicity. Measuring retinal thickness 1.0 mm from the foveal center in patients receiving these medications may help screen for early toxicity.