AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies.

Redox proteins thioredoxin 1 and thioredoxin 2 support retinal ganglion cell survival in experimental glaucoma.

We investigated the neuroprotective effect of thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) which play critical roles in the regulation of oxidative stress on retinal ganglion cells (RGCs) in a rat glaucoma model. Expression of Trx1 and Trx2 and Trx-interacting protein (Txnip) was observed in the RGC layer (GCL), nerve fiber layer and inner nuclear layer. Txnip-, Trx1- and Trx2-expressing cells in the GCL were primarily colocalized with RGCs. The increased Txnip protein level was observed 2 and 5 weeks after glaucoma induction. Trx1 level decreased 2 weeks after glaucoma induction and more prominently after 5 weeks. No change in Trx2 levels was detected. The effects of Trx1 and Trx2 overexpression on RGC survival were evaluated 5 weeks after glaucoma induction. In nontransfected and EGFP-transfected (used as a negative control) retinas, RGC loss was approximately 27% compared with control. The loss of RGCs in Trx1- and Trx2- transfected retinas was approximately 15 and 17%, respectively. Thus, Trx1 and Trx2 preserved 45 and 37% of cells, respectively that were destined to die in glaucomatous retinas. The results of this study provide evidence for the involvement of oxidative stress in RGC degeneration in experimental glaucoma and point to potential strategies to reduce its impact.

Advanced proliferative diabetic retinopathy in four young patients with flexion contractures (Rosenbloom syndrome).

In this report, we present four patients with type 1 diabetes of long duration (more than 20 years) who had multiple joint contractures (Rosenbloom syndrome) and who presented with reduced vision and advanced proliferative diabetic retinopathy. All of the cases had short stature which was non-familial and all had other microvascular complications (nephropathy and neuropathy). It seems that limited joint mobility (LJM) is a risk factor not only for microvascular complications, but also for more severe and advanced proliferative retinopathy.

Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema.

PURPOSE: To evaluate the additive effect of triamcinolone to bevacizumab in comparison to standard macular laser photocoagulation versus bevacizumab in the management of diabetic macular edema (DME). METHODS: In a prospective, randomized clinical trial, 130 eyes of 110 patients with type 2 diabetes with DME were included. Eligible eyes were randomly assigned to 1.25 mg intravitreal bevacizumab (42 eyes) (IVB group) or combination of 1.25 mg bevacizumab and 2 mg triamcinolone acetonide (41 eyes) (IVB+IVT group) or macular laser photocoagulation (47 eyes) (MPC). Central macular thickness (CMT) and visual acuity changes at week 6 and 16 were assessed. RESULTS: The mean age of the patients was 57 -/+7 years. Patients were followed 16 weeks. At week 6, all the three groups showed significant reduction in CMT but the reductions for IVB and IVB+IVT were significantly more than MPC (p<0.001). At week 16, the response was not stable for IVB (p<0.001), but IVB+IVT maintained its superior status to MPC (p<0.001). At week 16, visual acuities were essentially unchanged for the two groups of MPC and IVB and improvement for IVB+IVT was marginal and at most was 0.1 log MAR. No patient developed uveitis, endophthalmitis, or thromboembolic event. CONCLUSIONS: Single intravitreal bevacizumab or triamcinolone plus bevacizumab injection brought about significantly greater macular thickness reduction in diabetic patients in comparison to standard laser treatment. However, the response for bevacizumab alone was short-lived. Reduction in macular thickness was only marginally associated with visual acuity improvement in the triamcinolone plus bevacizumab injection group.

Intracameral tissue plasminogen activator to prevent severe fibrinous effusion after congenital cataract surgery.

BACKGROUND/AIMS: To evaluate the efficacy of intracameral recombinant tissue plasminogen activator (r-TPA) in prevention of fibrinous effusion after lensectomy, anterior vitrectomy, and posterior chamber intraocular lens (PCIOL) implantation in patients with congenital cataract. METHODS: The study was done as a double masked randomised clinical trial between April 2002 and November 2003 in Farabi Eye Hospital. 34 eyes of 26 patients with congenital cataract were included in the study and randomised into two groups (18 cases and 16 controls). Mean age was 8.1 years (3--14 years). Each eye underwent lensectomy and anterior vitrectomy with PCIOL implantation. At the end of surgery 20 microg r-TPA was injected intra-camerally in the case group. The control group received only balanced salt solution. All patients received periocular, systemic, and topical steroids after surgery. Patients underwent follow up examinations for 3 months. RESULTS: The incidence of intraocular fibrin membrane formation was significantly lower in the case group on days 1, 3, 7, 14 (p=0.02, p=0.01, p=0.01, and p=0.01, respectively, chi(2) test), but there was no significant difference on days 30 and 90. The frequency of pigmented intraocular lens precipitates was significantly lower in the case group at the end of the third month (p<0.001, chi(2) test). No gross ocular side effects were noted after r-TPA injection. CONCLUSION: It seems that prophylactic intracameral r-TPA is effective in prevention of fibrinous effusion at least in the first 2 weeks after cataract extraction in the paediatric age group and decreases the incidence of pigmented IOL precipitates.