Nogo-A in the visual system development and in ocular diseases.

Nogo-A is a potent myelin-associated inhibitor for neuronal growth and plasticity in the central nervous system (CNS). Its effects are mediated by the activation of specific receptors that intracellularly control cytoskeleton rearrangements, protein synthesis and gene expression. Moreover, Nogo-A has been involved in the development of the visual system and in a variety of neurodegenerative diseases and injury processes that can alter its function. For example, Nogo-A was shown to influence optic nerve myelinogenesis, the formation and maturation of retinal axon projections, and retinal angiogenesis. In adult animals, the inactivation of Nogo-A exerted remarkable effects on visual plasticity. Relieving Nogo-A-induced inhibition increased axonal sprouting after optic nerve lesion and axonal rewiring in the visual cortex of intact adult mice. This review aims at presenting our current knowledge on the role of Nogo-A in the visual system and to discuss how its therapeutic targeting may promote visual improvement in ophthalmic diseases.

Six3 regulates optic nerve development via multiple mechanisms.

Malformations of the optic nerve lead to reduced vision or even blindness. During optic nerve development, retinal ganglion cell (RGC) axons navigate across the retina, exit the eye to the optic stalk (OS), and cross the diencephalon midline at the optic chiasm en route to their brain targets. Many signalling molecules have been implicated in guiding various steps of optic nerve pathfinding, however much less is known about transcription factors regulating this process. Here we show that in zebrafish, reduced function of transcription factor Six3 results in optic nerve hypoplasia and a wide repertoire of RGC axon pathfinding errors. These abnormalities are caused by multiple mechanisms, including abnormal eye and OS patterning and morphogenesis, abnormal expression of signalling molecules both in RGCs and in their environment and anatomical deficiency in the diencephalic preoptic area, where the optic chiasm normally forms. Our findings reveal new roles for Six3 in eye development and are consistent with known phenotypes of reduced SIX3 function in humans. Hence, the new zebrafish model for Six3 loss of function furthers our understanding of the mechanisms governing optic nerve development and Six3-mediated eye and forebrain malformations.

Common embryological links to the optic pit and anterior segment structures.

PURPOSE: To analyze the anterior segment structures in patients with an optic disc pit to evaluate the common embryological links to the optic disc pit and anterior segment structures in these patients. METHODS: Ten patients with a unilateral optic disc pit detected during routine examination of the posterior pole and 15 healthy subjects as a control group underwent anterior segment analysis with Pentacam (Oculus, Inc., Wetzlar, Germany). Anterior segment parameters were compared between the eyes with an optic disc pit and fellow eyes of the patients and between the right and the left eyes of the healthy subjects. RESULTS: The anterior segment parameters of the eyes with an optic disc pit and fellow eyes of the patients were as follows, respectively: radius of the anterior corneal surface (7.68 +/- 0.28 and 7.71 +/- 0.28 mm), radius of the posterior corneal surface (6.36 +/- 0.28 and 6.43 +/- 0.28 mm), corneal thickness (532.40 +/- 31.32 and 530.20 +/- 28.51 micorm), corneal volume (58.86 +/- 3.72 and 58.42 +/- 3.37 mm), anterior chamber depth (3.28 +/- 0.80 and 2.98 +/- 0.39 mm), anterior chamber volume (178.00 +/- 36.48 and 168.30 +/- 38.14 mm), anterior chamber angle (39.30 +/- 6.00 and 36.52 +/- 5.66 degrees), and pupil diameter (3.15 +/- 0.64 and 2.96 +/- 0.47 mm). Only the back radius of corneal curvature was found to be statistically significantly lower in eyes with an optic disc pit (p = 0.025). The interocular comparison of anterior segment parameters in the healthy subjects showed no statistically significant difference (p > 0.05). CONCLUSIONS: The study demonstrates that those eyes with an optic disc pit have smaller back radius of corneal curvature compared with fellow eyes. Possibly, the embryological factors in the development of optic disc pit influence the development of cornea.

The effect of in ovo ethanol exposure on retina and optic nerve in a chick embryo model system.

Ocular anomalies seen in children with fetal alcohol syndrome (FAS) suggest that ocular structures are sensitive to alcohol exposure during their development. This study was designed to investigate the effect of in ovo ethanol (EtOH) exposure on retinal development and myelinization of optic nerve fibers at an ultra structural level in a chick embryo model system. Prior to incubation, fertilized chicken eggs were injected once with 100 microl of either 0.9% NaCl (vehicle control), or EtOH solutions at different doses (10, 30, or 50%, v:v in 0.9% NaCl) into their air sacs and incubated at 37.5 degrees C and saturation humidity. On day 20 embryos were analyzed in terms of their viability and growth and the optic cups including the optic nerves were dissected out. Specimens were processed for electron microscopy (EM). Results showed that, EtOH significantly decreased the viability of chick embryos (P < 0.045), and caused significant prenatal growth retardation (P < 0.004) in a dose-dependant manner. Light microscopy of semi thin sections revealed that prenatal exposure to EtOH resulted in both retinal degeneration and optic nerve hypoplasia (P < 0.001) in a dose-dependant manner. EM revealed that a dose-dependant decrease in the number of myelinated nerve fibers was profound in groups exposed to EtOH (P < 0.001). Furthermore, the myelin coats observed were thinner than those seen in control embryos. In groups exposed to EtOH myelin sheets were unorganized and contained vacuolar structures in between them. The tissue in between the cells and optic nerve fibers, on the other hand, lost its intact appearance with vacuolar and vesicular structures in between them. In addition, the optic nerve fibers contained granular accumulations in EtOH exposed groups. A dose dependent degeneration was also observed in retinas of EtOH exposed groups. The effect of EtOH was profound in pigment epithelium (PE), inner plexiform layer (IPL), and ganglion cell layer (GC). Mitochondrial deficiencies, and alterations in melanin granule number and distribution dominated the defects seen in PE. On the other hand, EM findings of all the affected layers were suggestive of induced cell death in EtOH exposed groups. Thus, this study suggests retinal development with the emphasis on melanin pigmentation in PE and optic nerve myelinization as potential targets of prenatal EtOH exposure and discusses potential mechanisms of EtOH action on these tissues.

Visual field defects in prematurely born patients with white matter damage of immaturity: a multiple-case study.

PURPOSE: White matter damage of immaturity may affect visual, motor and cognitive functions. This multiple-case study presents standardized perimetry results in six teenagers and young adults born prematurely with visual dysfunction due to white matter damage of immaturity of pre- or perinatal origin. METHODS: Six subjects, aged 13-25 years, born at a gestational age of 28-34 weeks, with white matter damage of immaturity documented by MRI, and optic disc appearances documented by fundus photography, were examined with manual and computerized quantitative perimetry. RESULTS: All subjects had subnormal visual field (VF) function, although the depth and extension of the VF defects differed between subjects. The inferior VF function was more deviant than the superior in all cases. The concordance between the VF defects detected with the different techniques was good, although the static computerized techniques revealed slightly more abnormality. CONCLUSION: White matter damage of immaturity may affect the VF. The lower VF is often more affected than the upper. The abnormalities can be demonstrated by both manual and computerized perimetry.

Neuroepithelial cyst in the optic nerve. Case report.

A 34-year-old woman presented with progressive loss of vision in her left eye of 2 months' evolution. Computerized tomography showed a hypodense lesion in the suprasellar region. At surgery a cystic lesion was found inside the optic nerve. Histological study proved it to be a neuroepithelial cyst. The pathogenesis of a neuroepithelial cyst in such an exceptional site is discussed.