The role of sensory innervation in cornea-lens regeneration.

BACKGROUND: Numerous sensory nerves in the cornea contribute to normal tissue homeostasis. Interestingly, cells within the basal corneal epithelium can regenerate new lenses in the frog, Xenopus. In this study, we investigated whether cornea sensory nerves or their neuropeptides are important for supporting cornea-lens regeneration. RESULTS: Attempts to sever the trigeminal nerve trunk, which provides sensory nerve branches to the cornea, did not inhibit lens regeneration. However, using this approach we found that it was not possible to completely disrupt sensory innervation, as these nerves are able to quickly regenerate back to the cornea. On the other hand, attenuation of neuropeptide levels with capsaicin was found to significantly inhibit lens regeneration, as visualized by a reduction of Substance P. These treatments also led to a reduction of cornea sensory innervation. Interestingly, inhibition of the Substance P-preferred receptor NK-1 with Spantide II did not affect lens-regeneration rates. CONCLUSIONS: This study provides evidence that cornea nerves support cornea-lens regeneration, which could occur through the release of various neurotrophic factors. Substance P, however, does not appear to be the critical component of this signaling pathway. Further studies are needed to investigate what role other known neurotrophic factors may play in this process.

Ion Channels in the Eye: Involvement in Ocular Pathologies.

The eye is the sensory organ of vision. There, the retina transforms photons into electrical signals that are sent to higher brain areas to produce visual sensations. In the light path to the retina, different types of cells and tissues are involved in maintaining the transparency of avascular structures like the cornea or lens, while others, like the retinal pigment epithelium, have a critical role in the maintenance of photoreceptor function by regenerating the visual pigment. Here, we have reviewed the roles of different ion channels expressed in ocular tissues (cornea, conjunctiva and neurons innervating the ocular surface, lens, retina, retinal pigment epithelium, and the inflow and outflow systems of the aqueous humor) that are involved in ocular disease pathophysiologies and those whose deletion or pharmacological modulation leads to specific diseases of the eye. These include pathologies such as retinitis pigmentosa, macular degeneration, achromatopsia, glaucoma, cataracts, dry eye, or keratoconjunctivitis among others. Several disease-associated ion channels are potential targets for pharmacological intervention or other therapeutic approaches, thus highlighting the importance of these channels in ocular physiology and pathophysiology.

Neuronal circuitry controlling the near response.

Experiments in primates have contributed greatly to our understanding of the neural mechanisms involved in the eye movements required to view objects at different distances. Early work focused on the circuitry for generating horizontal vergence eye movements alone. However, vergence eye movements are associated with lens accommodation and are usually accompanied by saccadic eye movements, so more recent work has been directed at understanding the interactions between vergence and accommodation, and between vergence and saccades. A new model explains the neural basis for interactions between vergence and accommodation by a neural network in which pre-motor elements are shared by these two systems. The effects of saccades on vergence eye movements appear to be the result of shared pre-motor circuits as well. Current evidence suggests that pontine omnipause neurons, known to be crucial for the generation of saccades, play an important role in the vergence pre-motor circuitry.

A projection of the lens accommodation-related area to the pupillo-constrictor area in the posteromedial lateral suprasylvian area in cats.

The fiber connection between areas related to lens accommodation and to pupillary constriction was studied in the posteromedial lateral suprasylvian area (PMLS) in the extrastriate cortex of the cat. The accommodation-related area was located in the PMLS by microstimulation, and the anterograde tracer Phaseolus vulgaris leucoagglutinin was injected into this area. Anterogradely-labeled fibers and terminals were found in the upper part of the medial bank of the middle suprasylvian sulcus, the area corresponding to the pupillo-constrictor area in the PMLS. The labeling was also found in the fundus of the middle suprasylvian sulcus, the medial bank of the lateral sulcus and the superficial layers of the superior colliculus. It is concluded that the area related to lens accommodation projects to the area related to pupillary constriction in the PMLS.

Cerebral cortical and brainstem areas related to the central control of lens accommodation in cat and monkey.

1. Studies on the central nervous system related to lens accommodation in cat and monkey were reviewed. 2. During the last decade, a considerable amount of neurophysiological data on the peripheral innervation of the ciliary muscle, properties of parasympathetic oculomotor neurons and mesencephalic reticular neurons have accumulated. 3. Neurophysiological and anatomical evidence supporting the contribution of the cerebellum to lens accommodation has been obtained. 4. Recently, cerebral cortical neurons in the parieto-occipital cortex with activities related to lens accommodation were found in cat and monkey.

Small-angle intraocular light scatter: a hypothesis concerning its source.

The crystalline lens makes a major contribution to intraocular light scatter, yet the responsible structural features have not been identified. A hypothesis is presented that implicates the fiber architecture of the ocular lens in small-angle scatter, this being the only part contributing to the associated reduction in vision. The main evidence supporting this hypothesis is a calculation of light scatter by a model lattice of fibers simulating the fiber lattice of the ocular lens. The results agree well with the angular dependence of measured intraocular scatter and, for reasonable parametric values, agree also with the measured magnitude.

Effect of optic nerve denervation on lens regeneration in adult newts, Triturus viridescens.

This experiment was designed to study the effect of optic nerve denervation on lens regeneration. Adult newts, Triturus viridescens, were divided into 4 groups: A) lentectomized newts, which served as controls, B) lentectomized newts with the optic nerve exposed and lightly palpated, C) newts with lens removed and the optic nerve cut simultaneously, and D) newts with lens removed first and optic nerve cut 7 days and 14 days later. Control animals required about 21 days to produce a new lens, and animals in group B demonstrated the same regeneration rate. In groups C and D, the regeneration rate was greatly retarded during the first 14 days. However, most of these animals regenerated a perfect new lens by 21 days postlentectomy.

Physiological identification of midbrain neurons related to lens accommodation in cats.

Single units were sought in the medial midbrain, whereas lens accommodation of the eye was monitored by using an infrared high-speed optometer. Nineteen of 135 units isolated were identified as accommodation-related units by two criteria: 1) they discharged in synchrony with spontaneously occurring accommodation, and b) the units were driven by stimulating the interpositus nucleus of the cerebellum. In eight other experiments, units were sought that were antidromically activated by stimulating parasympathetic preganglionic fibers to the ciliary ganglion. Eleven of 46 antidromically activated units were identified as accommodation-related units (accommodation-related oculomotor units). Accommodation-related oculomotor units were found in the medial midbrain within 1 mm of the midline. The majority of them were located lateral and dorsal to the Edinger-Westphal nucleus.

Cortical neurons related to lens accommodation in posterior lateral suprasylvian area in cats.

Cortical units were sought that discharged in temporal correlation with spontaneously occurring lens accommodation in the area surrounding the middle suprasylvian sulcus, between the stereotaxic coordinates A8.0 and P1.0, while monitoring lens accommodation by using an infrared optometer. Units were tentatively identified as accommodation related if their discharges were modulated before the onset times of lens accommodation. Forty-eight accommodation-related units were found. Modulation of discharges preceded the onset times of accommodation by 360 ms on the average. Most (95%) of these units were related to the increase in the refractive power of the lens. Antidromic activation from the dorsal midbrain was tested in 26 of 48 accommodation-related units. Fourteen (67%) units were antidromically activated from the superior colliculus and/or the pretectum. Nine (64%) of them were also activated antidromically from the lateral posterior nucleus of the thalamus. The location of these units were confirmed by histological reconstruction. They were found in the posterior medial and posterior lateral lateral suprasylvian (PMLS and PLLS) areas and in the transitional zone of PMLS to the suprasylvian gyrus, between stereotaxic coordinates A7.0 and A1.5.

Corneal sensitivity after epikeratophakia.

Corneal sensitivity was tested in 60 eyes of 30 patients who underwent unilateral epikeratophakia for the correction of aphakia (20 patients) or keratoconus (10 patients). Postoperative recovery time ranged from 2 months to 21 months (mean: 10 months). Our results indicate a relative hypesthesia of the epikeratophakia lenticule when compared with the peripheral host cornea and contralateral control cornea. However, corneal sensitivity tested in 11 patients with more than 1 year follow-up was increased compared with the sensitivity of 19 patients whose postoperative recovery was less than 1 year. Histopathologic findings in two lenticules from a nonhuman primate demonstrated sparse epithelial axon terminals. Host corneal nerves appear to innervate the lenticules by intraepithelial extension and by penetration of the superficial keratectomy scar.

Cortical neurons in and around the Clare-Bishop area related with lens accommodation in the cat.

Single-unit discharges in the cat Clare-Bishop area were correlated with spontaneous accommodation responses. No appreciable change was found in accommodation responses evoked by stimulating the Clare-Bishop area, when cerebellar outflow was blocked reversibly by cooling the superior cerebellar peduncle. It is suggested, therefore, that the Clare-Bishop area plays an important role in the lens accommodation system through a pathway independent from that of the cerebellum.

Mesencephalic neurons controlling lens accommodation in the cat.

Thirty units were found in the midbrain of the anesthetized cat which discharged in correlation with spontaneously occurring lens accommodation. The frequency of spike potentials increased before the onset of the accommodation response. Increased discharges were followed by a silent period. These units were driven orthodromically by stimulating the interpositus nucleus of the cerebellum and the posterior commissure. Eleven of these units were identified antidromically as parasympathetic oculomotor neurons.

The cerebellar control of accommodation of the eye in the cat.

The effect of cerebellar stimulation on the accommodation of the lens was examined in anesthetized cats. An infrared optometer was used to measure the refractive power of the lens during stimulation of the cerebellum. The area giving responses within latencies shorter than 160 msec and amplitudes larger than 0.15 diopters is localized in the contralateral interpositus and fastigial nuclei and the ipsilateral interpositus nucleus. No responses could be evoked by stimulating the bilateral lateral nuclei. Accommodation responses were also evoked by cerebellar cortex stimulation. Accommodation responses evoked by stimulating the cerebellar nuclei were inhibited by preceding cerebellar cortical stimulation.