Vesicular glutamate transporter 3 in age-dependent optic neuropathy.

PURPOSE: To determine retinal vesicular glutamate transporter 3 (VGLUT3) expression alterations in a mouse model of progressive optic neuropathy (glaucoma). METHODS: Tissue specimens were obtained from age-matched DBA/2J and control C57BL/6J mice for western blot analysis. Enucleated globes from DBA/2J, C57BL/6J, and BALB/cJ mice were fixed in formalin, paraffin-embedded, and sectioned for VGLUT3 protein localization. RESULTS: western blot analysis of the control retinas revealed the expression of a ~55 kDa immunoreactive VGLUT3 protein that is to be expected in tissues such as retina, brain, liver, heart, and kidney tissue, but not in intestinal or lung tissue. Furthermore, a strong ~130 kDa immunoreactive VGLUT3 isoform that is restricted to the central nervous system (the brain and retinas) was also identified in the controls, but was not detected in the DBA/2J retinas. Immunofluorescence microscopy showed a lack of VGLUT3 expression in the synapses between amacrine and retinal ganglion cells in DBA/2J retinas, in contrast to its strong expression in the C57BL/6J and BALB/cJ controls. CONCLUSIONS: Our results implicate the dysregulated expression of a central nervous system-specific VGLUT3 isoform as a predisposing factor in the development of optic neuropathy in DBA/2J mice, a spontaneous mouse model of glaucoma. In striking parallel to the visual system defects of glaucomatous DBA/2J mice, the inner ear of VGLUT3 knockout mice displays a progressive loss of inner hair cell to spiral-ganglion neuron synapses. A significant reduction in the number of spiral-ganglion neurons leads to age-associated deafness. Thus, we propose that the absence of this biochemically uncharacterized 130 kDa VGLUT3 isoform in the DBA/2J retina is a predisposing factor in synaptic instability, and a contributing factor in the age-dependent and progressive loss of ganglion cells projecting to the brain.

Bilateral simultaneous intravitreal injections in the office setting.

PURPOSE: To report the outcomes and complications of bilateral simultaneous intravitreal injections performed in the office. DESIGN: Retrospective case series. METHODS: Records of 35 patients receiving simultaneous bilateral intravitreal injections between November 2007 and November 2008 were reviewed. Data collected included indication for injection, preinjection and postinjection intraocular pressure (IOP), preinjection and postinjection visual acuity (VA), and complications/complaints after each injection. RESULTS: A total of 208 injections were administered to 35 patients, with a mean of 5.9 injections per patient (range, 2 to 14; standard deviation [SD], 3.68). One hundred and thirty-three eyes received bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) alone, 14 received bevacizumab plus preservative-free intravitreal triamcinolone or Triescence (Kenalog; Bristol-Myers Squibb Co, New York, New York, USA), 56 received ranibizumab (Lucentis; Genentech Inc), and 5 received bevacizumab plus dexamethasone (Decadron; Merck, Whitehouse Station, New Jersey, USA). Mean time of postinjection follow-up was 39 days. Postinjection VA follow-up measurements were available for 194 injections. The indication for initiating therapy was choroidal neovascularization from age-related macular degeneration (49 eyes), diabetic macular edema (ME) (13 eyes), proliferative diabetic retinopathy (4 eyes), ME attributable to retinal vein occlusion (2 eyes), and ME attributable to autoimmune retinopathy (2 eyes). The mean VA before each injection was 20/96 and at the next follow-up was 20/91 (P = .40). One patient had a painless, culture-negative endophthalmitis in 1 eye 3 days after bilateral bevacizumab; at 1 year VA improved from 20/400 to 20/80. CONCLUSIONS: Simultaneous bilateral intravitreal injections in the office are well tolerated. A separate povidone-iodine preparation, speculum, needle, and syringe were used for each eye. None of the patients requested alternating unilateral injections, after receiving bilateral injections. Patients should be counseled as to the risk of complications.