Shuichiro Hirahara

Areas of Nonperfusion in Peripheral Retina of Eyes With Pathologic Myopia Detected by Ultra-Widefield Fluorescein Angiography

PURPOSE We investigated the vascular system in the far peripheral retina in eyes with pathologic myopia by ultra-widefield fluorescein angiography (FA). METHODS We analyzed retrospectively 230 with pathologic myopia (myopic refractive error >8 diopters [D] or axial length >26.5 mm) and 42 emmetropic (refractive error < ± 2 D) controls who were examined with ultra-widefield FA by the Optos P200 system. Far peripheral retina was defined as the area anterior to the ampullae of the vortex veins. RESULTS Retinal capillary telangiectasia was observed in the far periphery of 34 of 42 (81.0%) emmetropic eyes and in 90 of 115 (78.3%) highly myopic eyes. Retinal capillary microaneurysms were observed in 13 of 42 (31.0%) emmetropic eyes and in 60 of 115 (52.2%) eyes with pathologic myopia. The differences in the incidences of these two lesions were not significant. Areas of nonperfusion in the far periphery were found in two of 42 (4.8%) emmetropic eyes and in 95 of 115 (82.6%) eyes with pathologic myopia. In these myopic eyes, the arterioles and venules had an abrupt ending, and in advanced cases, the perfused area was limited to just beyond the staphyloma border. None of the eyes developed retinal neovascularization. Statistical analyses showed that the highly myopic patients with avascular areas in the far periphery were significantly older, and had significantly longer axial length. CONCLUSIONS Areas of nonperfusion in the far periphery are common in eyes with pathologic myopia. Retinal vasculature in the far periphery is significantly altered in eyes with pathologic myopia, and this may be due to a mechanical stretching.

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D–dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.

Transient tractional retinal detachment in an eye with retinitis pigmentosa.

We present a case of retinitis pigmentosa with vitreoretinal traction-associated retinal detachment. The retinal detachment was detected in the nasal periphery. No retinal breaks and no active vascular leakage were observed by fundus scopy and fluorescein angiography, respectively. However, 8 months later, the tractional retinal detachment was spontaneously resolved with posterior vitreous detachment.

Suppression of Retinal Neovascularization by Anti-CCR3 Treatment in an Oxygen-Induced Retinopathy Model in Mice

Purpose: To investigate the association between retinal neovascularization and the CC chemokine receptor-3 (CCR3) in a mouse model of oxygen-induced retinopathy (OIR). Methods: An OIR model in C57BL/6J mice was used as a retinal neovascularization model. An enzyme-linked immunosorbent assay was performed to evaluate the chronological change in vascular endothelial growth factor A (VEGF-A) and eotaxin expressions. CCR3 and VEGF subtype expression in the retina was examined using real-time RT-PCR, and CCR3, eotaxin, VEGF-A, and CD31 expression was examined immunohistochemically. A CCR3 neutralizing antibody (Ab) was injected into the vitreous humor on both postnatal days 12 (P12) and 14 (P14). Retinal neovascularizations were quantified by measurement of the percentages of neovascular area. Results: The mean eotaxin and VEGF-A protein level was significantly downregulated at P10 and P12 and was significantly upregulated at P14 and P17 (p < 0.05). CCR3 mRNA expression was significantly upregulated at P12 (p < 0.05). VEGF164 mRNA expression was significantly upregulated at P14 (p < 0.05). The areas of vaso-obliteration and neovascularization were significantly suppressed in anti-CCR3 Ab-treated eyes (p < 0.05). Anti-CCR3 Ab treatment suppressed VEGF and eotaxin but not monocyte chemoattractant protein-1. And VEGF 164 mRNA but not VEGF120 mRNA was suppressed by anti-CCR3 Ab treatment. Conclusions: The present data suggest that anti-CCR3 treatment can suppress retinal neovascularization. Anti-CCR3 treatment may have potential as a new therapy for retinopathies with retinal neovascularization such as diabetic retinopathy and retinopathy of prematurity.

A case of retinopathy of prematurity treated by pattern scan laser photocoagulation

We experienced a case of retinopathy of prematurity that was successfully treated with pattern scan laser. Pattern scan laser treatment should be considered as one treatment option for Retinopathy of Prematurity.