Background/Aims: The trabecular meshwork (TM) tissue is constantly exposed to dynamic stress caused by intraocular pressure (IOP). The effects of such biomechanical stress on the TM have not been analyzed. This study developed an animal model of fluctuating IOP and evaluated the effects of these fluctuations on TM tissue. Methods: To create fluctuation in the IOP, one eye of adult SD rats was exposed to cyclic stress with IOP fluctuation ranging from 5 mmHg to 45 mmHg at a 1/60 Hz frequency for 30 minutes every day for several weeks. The other eye was not treated and served as the control. Hematoxylin-eosin staining was used to evaluate changes in the ganglion cells and the morphology, thickness and density of the TM; immunohistochemistry was used to detect α-smooth muscle actin (α-SMA), laminin (LA) and fibronectin (FN) expression in the TM. Results: After several weeks of daily IOP fluctuation, the TM thickness remained unchanged, whereas the density dramatically increased. α-SMA, LA and FN were expressed in rat TM tissue, and the percentages of areas with positive expression significantly increased. The IOP was similar in the treated and control eyes and only tended to increase on day 22 of the experiment. Throughout the 28-day experiment, no ganglion cells were lost. Conclusions: Large fluctuations in IOP promoted the synthesis of α-SMA, LA and FN in the TM and increased the density of the TM, suggesting that fluctuations in IOP can induce pathological changes in the TM.

Nogo-A is a myelin-derived inhibitor playing a pivotal role in the prevention of axonal regeneration. A functional domain of Nogo-A, Amino-Nogo, exerts an inhibitory effect on axonal regeneration, although the mechanism is unclear. The present study investigated the role of the Amino-Nogo-integrin signaling pathway in primary retinal ganglion cells (RGCs) with respect to axonal outgrowth, which is required for axonal regeneration. Immunohistochemistry showed that integrin αv, integrin α5 and FAK were widely expressed in the visual system. Thy-1 and GAP-43 immunofluorescence showed that axonal outgrowth of RGCs was promoted by Nogo-A siRNA and a peptide antagonist of the Nogo-66 functional domain of Nogo-A (Nep1-40), and inhibited by a recombinant rat Nogo-A-Fc chimeric protein (Δ20). Western blotting revealed increased integrin αv and p-FAK expression in Nogo-A siRNA group, decreased integrin αv expression in Δ20 group and decreased p-FAK expression in Nep1-40 group. Integrin α5 expression was not changed in any group. RhoA G-LISA showed that RhoA activation was inhibited by Nogo-A siRNA and Δ20, but increased by Nep1-40 treatment. These results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.

Background: Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo. Methods: Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated. Results: Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group. Conclusion: These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.

Bietti crystalline dystrophy can occur with bilateral macular holes, but the cause is unclear.

Previous studies have shown that Nogo-NgR system plays multiple roles in controlling axonal regeneration and neuronal plasticity. However, the investigation on the distributions of Nogo and NgR was limited to restricted areas or special ages, and their expression patterns in the neonatal visual nervous system is still unknown. Frozen sections were made from eyeballs and brains of three neonatal rats, and expression of Nogo and NgR proteins were examined by immunofluorescence under a laser confocal microscopy. Nogo and NgR were observed to express in the cell bodies of retina, lateral geniculate bodies and visual cortex of the neonatal rats. Our results provide evidences that the Nogo-NgR system may play an active role in the plasticity of neonatal visual system.