Biological modulation of corneal epithelial wound healing / Modulação biológica do processo de cicatrização epitelial da córnea

ABSTRACT The transparency and maintenance of corneal epithelial integrity are essential for its optical properties and, to preserve these characteristics, the epithelium undergoes continuous renewal. This renewal depends on the control of cell proliferation and differentiation mediated by mitogenic factors responsible for increasing mitoses and stimulating cellular migration. Cell-cell communication plays a pivotal role in epithelial healing process, and several cytokines and growth factors are involved in this process. Understanding the cross-talk and paracrine effects of these cytokines and growth factors released can help in the search for new therapeutic strategies to treat ocular surface diseases.

RESUMO A transparência e a manutenção da integridade epitelial da córnea são essenciais para suas propriedades ópticas e, para preservar tais características, o epitélio sofre renovação contínua. Essa renovação depende do controle da proliferação e diferenciação celular mediadas por fatores mitogênicos responsáveis pelo aumento das mitoses e estímulo à migração celular. A comunicação célula-célula desempenha um papel fundamental no processo de cicatrização epitelial, e várias citocinas e fatores de crescimento estão envolvidos neste processo. Compreender os efeitos cruzados e paracrinos dessas citocinas e fatores de crescimento liberados pode ajudar na busca de novas estratégias terapêuticas para o tratamento de doenças da superfície ocular.

A supramolecular look at microenvironmental regulation of limbal epithelial stem cells and the differentiation of their progeny / Uma visão supramolecular sobre a regulação microambiental de células tronco epiteliais limbais e a diferenciação de sua progênie

ABSTRACT Various approaches have been taken to improve our knowledge of the microenvironmental regulation of limbal epithelial stem cells. Researchers have extensively investigated the roles of growth factors, survival factors, cytokines, enzymes, and permeable molecules secreted by the limbal cells. However, recent evidence suggests that stem cell fate (i.e., self-renewal or differentiation) can also be influenced by biophysical and mechanical cues related to the supramolecular organization and the liquid crystalline (mesophase) nature of the stromal extracellular matrix. These cues can be sensed by stem cells and transduced into intracellular biochemical and functional responses, a process known as mechanotransduction. The objective of this review is to offer perspectives on the supramolecular microenvironmental regulation of limbal epithelial stem cells and the differentiation of their progeny.

RESUMO Muitas abordagens têm sido utilizadas para ampliar entendimentos sobre a regulação microambiental das células tronco epiteliais limbais. Neste contexto, pesquisadores têm exaustivamente investigado a participação de fatores de crescimento, fatores de sobrevida, citocinas, enzimas e moléculas permeáveis secretadas pelas células limbais. Entretanto, evidências recentes sugerem que o destino (ie. autorrenovação ou recrutamento para a via de diferenciação) das células tronco também sofre influência de estímulos biofísicos ou mecânicos relacionados à organização supramolecular e à natureza liquido-cristalina (mesofases) da matriz extracelular estromal. Esses estímulos podem ser percebidos e traduzidos pelas células tronco em sinais bioquímicos que geram respostas funcionais, através de um processo designado de mecanotransdução. Objetiva-se, com a presente revisão, oferecer ao leitor perspectivas supramoleculares sobre a regulação microambiental das células tronco epiteliais limbais e a diferenciação de sua progênie.

Maintenance of the corneal epithelium is carried out by germinative cells of its basal stratum and not by presumed stem cells of the limbus

The purpose of this investigation was to analyze the proliferative behavior of rabbit corneal epithelium and establish if any particular region was preferentially involved in epithelial maintenance. [3H]-thymidine was injected intravitreally into both normal eyes and eyes with partially scraped corneal epithelium. Semithin sections of the anterior segment were evaluated by quantitative autoradiography. Segments with active replication (on) and those with no cell division (off) were intermingled in all regions of the tissue, suggesting that the renewal of the epithelial surface of the cornea followed an on/off alternating pattern. In the limbus, heavy labeling of the outermost layers was observed, coupled with a few or no labeled nuclei in the basal stratum. This suggests that this region is a site of rapid cell differentiation and does not contain many slow-cycling cells. The conspicuous and protracted labeling of the basal layer of the corneal epithelium suggests that its cells undergo repeated cycles of replication before being sent to the suprabasal strata. This replication model is prone to generate label-retaining cells. Thus, if these are adult stem cells, one must conclude that they reside in the corneal basal layer and not the limbal basal layer. One may also infer that the basal cells of the cornea and not of the limbus are the ones with the main burden of renewing the corneal epithelium. No particular role in this process could be assigned to the cells of the basal layer of the limbal epithelium.

Estudo comparativo entre desepitelização mecânica e química na ceratectomia fotorrefrativa - sintomatologia e re-epitelização pós-operatória / Comparison between mechanical and chemical epithelial removal on photorrefractive keratectomy - symptoms and post-operative epithelial healing

OBJETIVO: Comparar os pacientes submetidos à ceratectomia fotorrefrativa com desepitelização mecânica versus química quanto ao tipo e severidade dos sintomas e quanto ao tempo de re-epitelização. MÉTODOS: Determinamos a intensidade e tipo dos sintomas referidos pelos pacientes submetidos ao PRK, submetidos a uma técnica de desepitelização em cada olho, de forma aleatória e simples-cego. Conjuntamente, estudamos a epitelização corneana no quinto dia pós-operatório, observando se um possível atraso desta interferiria nos sintomas observados. RESULTADOS: Sete pacientes (10,3 por cento) não apresentaram sintomas em ambos os olhos. A desepitelização química mostrou maior frequência de sintomas quando analisados em relação aos pacientes que apresentaram sintomas somente em um olho [N=20 (29,4 por cento) versus N=3 (4,4 por cento)]. Quando os sintomas foram observados em ambos os olhos, foram maiores nos olhos submetidos a desepitelização química [N=21 (30,9 por cento) versus N=8 (11,8 por cento)]. Obtivemos p<0,001 na avaliação geral dos pacientes e seus sintomas. CONCLUSÃO: Neste estudo, observamos que a desepitelização química com álcool a 20 por cento gera mais sintomas que a mecânica no PRK simultâneo de ambos os olhos.

OBJECTIVE: To compare, among patients subjected to PRK, the types and intensity of its post-operative symptoms, between mechanical versus chemical epithelial removal, as well as epithelial healing time. METHODS: We compare the frequency and intensity of referred symptoms by patients that underwent PRK, where each eye underwent one of the different epithelial removal techniques, randomly chosen and in simple-blind format. Additionally, we studied corneal epithelial healing on the fifth postoperative day, in order to observe whether an eventual delay on epithelial healing could interfere on the observed symptoms. RESULTS: Seven patients (10,3 percent) showed no symptoms on both eyes. Chemical removal showed higher symptom rate among patients with symptoms in only one eye [N=20 (29,4 percent) versus N=3 (4,4 percent)]. Among patients with symptoms in both eyes, these were higher on eyes submitted to chemical removal [N=21 (30,9 percent) versus N=8 (11,8 percent)]. Values were statistically significant (p<0,001). CONCLUSION: In this study, we observed that chemical epithelial removal with alcohol at 20 percent causes more symptoms than mechanical in patients undergoing simultaneous PRK in both their eyes.

Amniotic membrane transplantation in ocular surface disorders.

The term ocular surface disorders indicate a close relationship between the conjunctival and corneal epithelium in many corneal and external diseases. The human amniotic membrane has a thick basement membrane and an avascular stromal matrix and its first ophthalmic use was reported by deRoth for conjunctival surface reconstruction. It was subsequently used for different ophthalmic reasons. Amniotic membrane transplantation can be used in a number of conditions eg, as a graft to replace damaged ocular surface stromal matrix or as a patch to prevent unwanted inflammatory insults from gaining access to the damaged ocular surface. Amniotic membrane can be utilised in persistent of recurrent corneal epithelial and stromal defects; in cases of corneal perforation due to ulcer or melting; after conjunctival excision for acquired melanosis, neoplasia, etc; in cases of pemphigoid, Stevens-Johnson syndrome, chemical bums; in cases of symblepharon, in dry eyes or in large leaking filtering blebs.

Corneal epithelial wound healing.

One of the important functions of the cornea is to maintain normal vision by refracting light onto the lens and retina. This property is dependent in part on the ability of the corneal epithelium to undergo continuous renewal. Epithelial renewal is essential because it enables this tissue to act as a barrier that protects the corneal interior from becoming infected by noxious environmental agents. The renewal process also maintains the smooth optical surface of the cornea. This rate of renewal is closely maintained by an integrated balance between the processes of corneal epithelial proliferation, differentiation, and cell death. Attempts to understand this complex cascade make it evident that the appropriate integration and coordination of corneal epithelial renewal depends on the actions of a myriad of cytokines. We have attempted in this review to collate the receptor and cell signaling events and cytokine studies that are responsible for mediating corneal wound healing.