Background: Patching an eye for a period of 2 hours results in a period of plasticity where inter-ocular balance shifts in favor of the patched eye. Acetylcholine has been shown to improve visual function and augment adult neural plasticity. Here we evaluate whether administering the cholinesterase inhibitor donepezil enhances the magnitude or duration of the patching induced shift in ocular balance.
Methods: We used a double-blind drug treatment design to test the effect of donepezil and patching on the shift in ocular balance. We used a well-known binocular phase combination task to measure ocular balance before and after treatment.
Results: Our results demonstrate that donepezil does not enhance, and may actually reduce the magnitude and duration of the patching-induced shift in ocular balance.
Conclusions: Patching induced adult neural plasticity does not appear to be modulated by the cholinergic system, however, increased dose or longer drug administration periods may yield significant results. Future studies on binocular rivalry are in the pipeline.
Background: Visual deficits, caused by ocular disease or trauma to the visual system, can cause lasting damage with insufficient treatment options available. However, recent research has focused on neural plasticity as a means to regain visual abilities. In order to better understand the involvement of neural plasticity and reorganization in partial vision restoration, we aim to evaluate the partial recovery of a visual deficit over time using three behavioural tests. In our study, a partial optic nerve crush (ONC) serves as an induced visual deficit, allowing for residual vision from surviving cells.
Methods: Three behavioural tests—optokinetic reflex, object recognition, and visual cliff—were conducted in 9 mice prior to a bilateral, partial ONC, then 1, 3, 7, 14, 21, and 28 days after the ONC. The optokinetic reflex test measured the tracking reflex in response to moving sinusoidal gratings. These gratings increase in spatial frequency until a reflex is no longer observed, i.e., a visual acuity threshold is reached. The object recognition test examines the animal’s exploratory behaviour in its capacity to distinguish high versus low contrast objects. The visual cliff test also evaluates exploratory behaviour, by simulating a cliff to observe the animal’s sense of depth perception. All three tests provide an estimate of the rodent’s visual abilities at different levels of the visual pathway.
Results: The partial optic nerve crush resulted in a total loss of visual acuity as measured by the optokinetic reflex. The deficit did not show improvement during the 4 following weeks. Despite the visual cliff test showing a non-significant decrease in deep end preference 1-day post ONC, though this was not the case for subsequent test occasions. The object recognition test showed no significant trends.
Conclusions: In conclusion, the optokinetic reflex test showed a significant loss of function following the visual deficit, but no recovery. However, a complimentary pilot study shows visual recovery using lighter crush intensities. The spatial visual function does not seem to be affected by the ONC, suggesting that the object recognition and visual cliff tests, in their current design, may rely on somatosensory means of exploration.
Background: Overexpression of inducible nitric oxide synthase (iNOS) has been reported in diabetic retinopathy (DR). The kinin B1 receptor (B1R) is also overexpressed in DR, and can stimulate iNOS via Gαi/ERK/MAPK pathway. We previously showed that the topical administration of a B1R antagonist, LF22-0542, significantly reduces leukocyte infiltration, increased vascular permeability and overexpression of several inflammatory mediators, including iNOS in DR. Thus, the aim of this study was to determine whether the pro-inflammatory effects of B1R are attributed to oxidative stress caused by the activation of iNOS pathway in order to identify new therapeutic targets for the treatment of DR. iNOS and B1R being absent in the normal retina, their inhibition is unlikely to result in undesirable side effects. The approach will be no invasive by eye application of drops.
Methods: Diabetes was induced in male Wistar rats (200–230 g) by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg b.w). One week later, rats were randomly divided into four groups (N=5) and treated for one week as follows: Gr 1: control rats treated with the selective iNOS inhibitor (1,400 W, 0.06 μM twice a day by eye-drops ×7 days), Gr 2, STZ-diabetic rats treated with 1,400 W, Gr 3: control rats received a selective B1R agonist [Sar (D-Phe8)-des-Arg9-BK, 100 μg twice a week] by intravitreal injections (itrv) and treated with 1,400 W, Gr 4: STZ-diabetic rats + B1R agonist +1,400 W. At the end of treatment and two weeks post-STZ, three series of experiments were carried out to measure vascular permeability (by Evans blue dye method) and the expression of vasoactive and inflammatory mediators, including iNOS, VEGF-A, VEGF-R2, IL-1β, Cox-2, TNF-α, bradykinin 1 and 2 receptors and carboxypeptidase M/kininase 1 (by Western Blotting and qRT-PCR). The nitrosative stress (nitrosylation of proteins) was also assessed by Western Blotting. One-way Anova test with Bonferroni post hoc was used for statistical analysis.
Results: STZ-diabetic rats showed a significant increase in retinal vascular permeability (22.8 μg/g Evans blue dye per g of fresh retinas, P=0.016) compared with control rats and control treated rats (17.2 and 16.8 μg/g respectively). The injections of B1R agonist amplified the increase of vascular permeability which was normalized by the 1,400 W. The overexpression of inflammatory markers was also normalized by the 1,400 W in STZ-diabetic rats received or not the B1R agonist.
Conclusions: These results support a contribution of iNOS in the deleterious effects of B1R in this model of diabetic retinopathy. Hence, iNOS inhibition by ocular application of 1,400 W may represent a promising and non-invasive therapeutic approach in the treatment of diabetic retinopathy.
Background: The neovascular aged-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly. It is presently treated by anti-VEGF intravitreal injection in order to stop the neovascularization. In seeking of more efficient treatments to prevent retinal damage, it has been proposed that the kinin-kallikrein system (KKS), a key player in inflammation, could be involved in AMD etiology. However, the role of kinin receptors and their interaction with VEGF in AMD is poorly understood.
Methods: In order to address this question, choroidal neovascularization (CNV) was induced in the left eye of Long-Evans rat. After laser induction, anti-VEGF or IgG control were injected into the vitreal cavity. Gene expression was measured by qRT-PCR, retinal adherent leukocytes were labelled with FITC-Concanavalin A lectin, vascular leakage by the method of Evans blue and cellular localisation by immunohistochemistry.
Results: The number of labelled adherent leucocytes was significantly increased in laser-induced CNV compared to the control eye. This was significantly reversed by one single injection of anti-VEGF. Extravasation of Evans blue dye was significantly increased in laser-induced CNV eyes compared to control eyes and partially reversed by one single injection of anti-VEGF or by R954 treatment. The mRNA expression of inflammatory mediators was significantly increased in the retina of CNV rats. Immunodetection of B1R was significantly increased in CNV eyes. B1R immunolabeling was detected on endothelial and ganglion cells.
Conclusions: This study is the first to highlight an effect of the kinin/kallikrein system in a model of CNV that could be reduced by both anti-VEGF therapy and topically administered B1R antagonist R-954.
