Temperature-Sensitive Transient Receptor Potential Channels in Corneal Tissue Layers and Cells

We here provide a brief summary of the characteristics of transient receptor potential channels (TRPs) identified in corneal tissue layers and cells. In general, TRPs are nonselective cation channels which are Ca ²⁺ permeable. Most TRPs serve as thermosensitive molecular sensors (thermo-TRPs). Based on their functional importance, the possibilities are described for drug-targeting TRP activity in a clinical setting. TRPs are expressed in various tissues of the eye including both human corneal epithelial and endothelial layers as well as stromal fibroblasts and stromal nerve fibers. TRP vanilloid type 1 (TRPV1) heat receptor, also known as capsaicin receptor, along with TRP melastatin type 8 (TRPM8) cold receptor, which is also known as menthol receptor, are prototypes of the thermo-TRP family. The TRPV1 functional channel is the most investigated TRP channel in these tissues, owing to its contribution to maintaining tissue homeostasis as well as eliciting wound healing responses to injury. Other thermo-TRP family members identified in these tissues are TRPV2, 3 and 4. Finally, there is the TRP ankyrin type 1 (TRPA1) cold receptor. All of these thermo-TRPs can be activated within specific temperature ranges and transduce such inputs into chemical and electrical signals. Although several recent studies have begun to unravel complex roles for thermo-TRPs such as TRPV1 in corneal layers and resident cells, additional studies are needed to further elucidate their roles in health and disease

Therapeutic Penetrating Keratoplasty in a Case of Corneal Perforation Caused by <i>Colletotrichum gloeosporioides</i> Infection

Background: Corneal infection of Colletotrichum gloeosporioides is uncommon and usually limited to the anterior stroma. However, we observed a case of corneal stromal perforation caused by this fungus under a compromised condition. Case: A 73-year-old woman consulted us with a severe corneal ulceration. She was a tangerine orange farmer who suffered from rheumatoid arthritis for more than ten years. Before consultation with us, she received pterygium excision in her right eye. She then developed a corneal ulceration and received topical glucocorticoid therapy upon diagnosis of rheumatoid arthritis-related stromal ulcer in the eye. At the first consultation with us, a corneal ulceration was observed in the inferotemporal area of her right cornea. Biological examination detected a filamentous fungus, Colletotrichum gloeosporioides. Topical and systemic antifungal treatments were not significantly effective. Fourteen days after consultation, the lesion grew worse, leading to stromal perforation, which was treated by therapeutic penetrating keratoplasty using a preserved corneal button. Conclusions: Topical glucocorticoid could accelerate the growth of Colletotrichum gloeosporioides before diagnosis, even though the primary cause of corneal ulceration development might be rheumatoid arthritis

A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia

Background. Epithelial dysplasia is categorized as conjunctival/corneal intraepithelial neoplasia which is a precancerous lesion. The lesion is usually developed at the limbal region and grows towards central cornea in association with neovascularization into the lesion. Here, we report a case of isolated nonvascularized corneal epithelial dysplasia surrounded by normal corneal epithelium with immune histochemical finding of ocular surface tissues cytokeratins, for example, keratin 13 and keratin 12. Case Presentation. A 76-year-old man consulted us for visual disturbance with localized opacification of the corneal epithelium in his left eye. His visual acuity was 20/20 and 20/200 in his right and left eye, respectively. Slit lamp examination showed a whitish plaque-like lesion at the center of his left corneal epithelium. No vascular invasion to the lesion was found. The lesion was surgically removed and subjected to histopathological examination and diagnosed as epithelial dysplasia. Amyloidosis was excluded by direct fast scarlet 4BS (DFS) staining. Immunohistochemistry showed that the dysplastic epithelial cells express keratin 13 and vimentin, but not keratin 12, indicating that the neoplastic epithelial cells lacked corneal-type epithelium differentiation. Conclusions. The lesion was diagnosed as nonvascularized epithelial dysplasia of ocular surface. Etiology of the lesion is not known

Ocular surface inflammation impairs structure and function of meibomian gland

Dysfunction of the meibomian glands alters secreted meibum quantitatively and qualitatively that can lead to damage to the ocular surface epithelium. In response to an unstable tear film cause by meibomian gland dysfunction, ocular surface epithelium is damaged and expresses inflammatory cytokines leading to secondary ocular inflammation. In turn, inflammatory disorders of the palpebral conjunctiva and lid margin may affect the structure and function of meibomian gland. The disorders include allergic conjunctivitis, long-term usage of contact lenses, dermatological diseases that affect conjunctival homeostasis, Stevens-Johnson's syndrome or chemical burning of the ocular surface and lid margin

Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse Cornea

To investigate the effects of loss of transient receptor potential vanilloid receptor 1 (TRPV1) on the development of neovascularization in corneal stroma in mice. Blocking TRPV1 receptor did not affect VEGF-dependent neovascularization in cell culture. Lacking TRPV1 inhibited neovascularization in corneal stroma following cauterization. Immunohistochemistry showed that immunoreactivity for active form of TGFβ1 and VEGF was detected in subepithelial stroma at the site of cauterization in both genotypes of mice, but the immunoreactivity seemed less marked in mice lacking TRPV1. mRNA expression of VEGF and TGFβ1 in a mouse cornea was suppressed by the loss of TRPV1. TRPV1 gene ablation did not affect invasion of neutrophils and macrophage in a cauterized mouse cornea. Blocking TRPV1 signal does not affect angiogenic effects by HUVECs in vitro. TRPV1 signal is, however, involved in expression of angiogenic growth factors in a cauterized mouse cornea and is required for neovascularization in the corneal stroma in vivo

Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse Cornea

To investigate the effects of loss of transient receptor potential vanilloid receptor 1 (TRPV1) on the development of neovascularization in corneal stroma in mice. Blocking TRPV1 receptor did not affect VEGF-dependent neovascularization in cell culture. Lacking TRPV1 inhibited neovascularization in corneal stroma following cauterization. Immunohistochemistry showed that immunoreactivity for active form of TGF 1 and VEGF was detected in subepithelial stroma at the site of cauterization in both genotypes of mice, but the immunoreactivity seemed less marked in mice lacking TRPV1. mRNA expression of VEGF and TGF 1 in a mouse cornea was suppressed by the loss of TRPV1. TRPV1 gene ablation did not affect invasion of neutrophils and macrophage in a cauterized mouse cornea. Blocking TRPV1 signal does not affect angiogenic effects by HUVECs in vitro. TRPV1 signal is, however, involved in expression of angiogenic growth factors in a cauterized mouse cornea and is required for neovascularization in the corneal stroma in vivo

Ocular surface alkali injury damages meibomian glands in mice

PurposeTo examine effects of alkali injury of the ocular surface on meibomian gland pathology in mice.MethodsThree μL of 1&nbsp;N NaOH were applied under general anesthesia to the right eye of 10-week-old BALB/c (n&nbsp;=&nbsp;54) mice to produce a total ocular surface alkali burn. The meibomian gland morphology was examined at days 1, 2, 5, 10, and 20 by stereomicroscopy and non-contact infrared meibography. Mice were then sacrificed and eyelids processed for histology with hematoxylin-eosin and immunohistochemistry for ELOVL4, PPARγ, myeloperoxidase (a neutrophil marker) and F4/80 macrophage antigen, as well as TUNEL staining. Another set of specimens was processed for cryosectioning and Oil red O staining.ResultsAlkali injury to the ocular surface produced cellular apoptosis, infiltration of neutrophils and macrophages, degeneration of the meibomian gland, and ductal dilation. Inflammation in and destruction of acunal stricture seemed more prominent in the lower eyelid, while duct dilation was more frequently observed in the upper eyelid during healing. Surviving acinar cells were labeled for ELOVL4 and PPARγ. Oil red O staining showed that the substance in the dilated duct contained predominantly neutral lipid.ConclusionsAlkali injury to the ocular surface results in damage and destruction of the eyelid meibomian glands. The pattern of the tissue damage differs between glands of the upper and lower eyelids