Low glucose under hypoxic conditions induces unfolded protein response and produces reactive oxygen species in lens epithelial cells

Aging is enhanced by hypoxia and oxidative stress. As the lens is located in the hypoglycemic environment under hypoxia, aging lens with diabetes might aggravate these stresses. This study was designed to examine whether low glucose under hypoxic conditions induces the unfolded protein response (UPR), and also if the UPR then generates the reactive oxygen species (ROS) in lens epithelial cells (LECs). The UPR was activated within 1 h by culturing the human LECs (HLECs) and rat LECs in <1.5 mM glucose under hypoxic conditions. These conditions also induced the Nrf2-dependent antioxidant-protective UPR, production of ROS, and apoptosis. The rat LECs located in the anterior center region were the least susceptible to the UPR, whereas the proliferating LECs in the germinative zone were the most susceptible. Because the cortical lens fiber cells are differentiated from the LECs after the onset of diabetes, we suggest that these newly formed cortical fibers have lower levels of Nrf2, and are then oxidized resulting in cortical cataracts. Thus, low glucose and oxygen conditions induce the UPR, generation of ROS, and expressed the Nrf2 and Nrf2-dependent antioxidant enzymes at normal levels. But these cells eventually lose reduced glutathione (GSH) and induce apoptosis. The results indicate a new link between hypoglycemia under hypoxia and impairment of HLEC functions

Multimodal imaging in handheld laser-induced maculopathy

PURPOSE: To describe the clinical and imaging findings in 3 patients with maculopathy secondary to handheld laser exposure. DESIGN: Retrospective, observational case series. METHODS: We evaluated the multimodal imaging including fundus autofluorescence and spectral-domain optical coherence tomography (OCT) for 3 patients with histories of exposure to handheld lasers. RESULTS: An 18-year-old woman with a history of repetitive self-inflicted handheld laser exposure was found to have bilateral outer retinal streaks in the macula and the superior peripheral retina on both ophthalmoscopy and multimodal imaging. Initial spectral-domain OCT revealed vertical hyper-reflective bands at the level of the outer retina corresponding to the streaks. An 11-year-old boy who played with a green laser developed a yellow foveal lesion and outer retinal streaks in the superior macula. Spectral-domain OCT showed vertical hyper-reflective bands in the outer retina corresponding to the streaks. A 14-year-old boy developed bilateral focal foveal lesions and ellipsoid loss on spectral-domain OCT following peer-inflicted laser injury. CONCLUSIONS: In a series of 3 patients, outer retinal streaks were associated with self-inflicted handheld laser injury. In contrast, accidental and peer-inflicted laser injuries were found to result in focal foveal lesions

Type 3 neovascularization: The expanded spectrum of retinal angiomatous proliferation

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A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes

Objective: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. Design: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. Setting: Four ophthalmic centers in Europe and North America providing retinal care. Participants: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. Methods: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. Results: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. Conclusions: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD