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      Clinical evaluation and induced corneal vascularization study by native and anionic collagen membranes in rabbits corneas Translated title: Avaliação clínica e estudo da vascularização corneal induzida pelas membranas de colágeno nativo e aniônico em córneas de coelhos

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          PURPOSE: To evaluate the corneal vascularization (CV) and the clinical aspects induced by interlamellar graft with native (NCM) and anionic (ACM) collagen membranes in rabbits corneas. METHODS: An interlamellar graft with a 0.25 x 0.25 cm NCM (group 1) or ACM (group 2) fragment was performed in the right eye (treated eye). In the left eye, an estromal tunnel was done (control eye). Sixteen rabbits were used, and they were subdivided into two experimental groups of eight animals each. The clinical evaluation was performed at the 1st, 3rd, 7th, 15th and 30th postoperative days. Corneal vascularization analysis was performed after 30 days by the Images Analizator System Leica Qwin-550®. RESULTS: After 7 days, corneal vascularization was observed at about 2.25 ± 0.71 mm (NCM) and at about 1.0 ± 1.69 mm (ACM), respectively, from the limbus in direction to the central cornea. After 15 days, CV increased in both groups (5.25 ± 1.03 mm - NCM; 2.0 ± 2.39 mm - ACM) and then progressively decreased until day 30 (2.25 ± 2.10 mm - NCM; 0.75 ± 2.12 mm - ACM). The statistical analysis indicated that the averages of the distances from the limb vessels to the grafts observed after 7 and 15 days had not differed statistically (p=0.17), and after 15 and 30 postoperative days had a tendency to differ statistically (p=0.09). The control eyes did not present any changes. CONCLUSION: The interlamellar graft with native and anionic collagen membranes induced corneal vascularization when applied to rabbit corneas, but anionic collagen membrane induced a smaller corneal vascularization when compared to native collagen membrane. Although further studies are required, the results found in this study demonstrated the usefulness of interlamellar graft with native and anionic collagen membranes in keratoplasties. These membranes consists in one more graft option for the surgical treatment of corneal repair in rabbits and others animals, when other forms of medical and surgical treatment are not effective.

          Translated abstract

          OBJETIVO: Avaliar os aspectos clínicos e vascularização corneal (VC) induzida pelo enxerto interlamelar das membranas de colágeno nativo (MCN) e de colágeno aniônico (MCA) em córneas de coelhos. MÉTODOS: Um fragmento com 0,25 x 0,25 cm de MCN (grupo 1) e MCA (grupo 2) foi realizado no olho direito (olho tratado) por enxertia interlamelar. No olho esquerdo (olho controle) foi realizado apenas um túnel estromal. No olho direito (olho controle) foi realizado apenas um túnel estromal. Dezesseis coelhos foram utilizados e foram divididos em dois grupos experimentais composto por oito animais cada. A avaliação clínica foi realizada aos 1, 3, 7, 15 e 30 dias de pós-operatório. A análise da vascularização corneal foi realizada após 30 dias pelo Sistema de analisador de imagens Leica Qwin-550®. RESULTADOS: Após 7 dias, a vascularização corneal do limbo em direção central da córnea observada foi de 2,25 ± 0,71 mm (MCN) e 1,0 ± 1,69 mm (ACM), respectivamente. Após 15 dias a vascularização corneal aumentou em ambos os grupos (5,25 ± 1,03 mm - MCN; 2,0 ± 2,39 mm - MCA), diminuindo até o 30º dia (2,25 ± 2,10 mm - MCN; 0,75 ± 2,12 mm - MCA). A análise estatística indicou que as médias das distâncias dos vasos do limbo em direção ao enxerto observadas após 7 e 15 dias não diferiram estatisticamente (p=0,17), e 15 e 30 dias de pós-operatório houve tendência a diferir estatisticamente (p=0,09). Os olhos controles não apresentaram nenhuma alteração. CONCLUSÃO: As membranas de colágeno nativo e de colágeno aniônico induzem a vascularização corneal quando aplicadas na córnea de coelhos por meio de enxertia interlamelar, mas membrana de colágeno ativo induz a pequena vascularização corneal quando comparada à membrana de colágeno aniônico. Embora estudos adicionais sejam necessários, os resultados encontrados no presente estudo demonstraram que as membranas de CN e CA possam ser úteis em ceratoplastias. Estas membranas consistem em mais uma opção de enxerto para o tratamento cirúrgico de reparo da córnea em coelhos e outros animais, quando não há resolução com outras formas de tratamento médico e cirúrgico.

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          Most cited references 28

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          Biomedical applications of collagen.

          Collagen is regarded as one of the most useful biomaterials. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenecity, made collagen the primary resource in medical applications. The main applications of collagen as drug delivery systems are collagen shields in ophthalmology, sponges for burns/wounds, mini-pellets and tablets for protein delivery, gel formulation in combination with liposomes for sustained drug delivery, as controlling material for transdermal delivery, and nanoparticles for gene delivery and basic matrices for cell culture systems. It was also used for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and valves. This article reviews biomedical applications of collagen including the collagen film, which we have developed as a matrix system for evaluation of tissue calcification and for the embedding of a single cell suspension for tumorigenic study. The advantages and disadvantages of each system are also discussed.
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            Interleukin-8. A corneal factor that induces neovascularization.

            A rabbit corneal pocket model was used to demonstrate that physiologic concentrations of human recombinant (r) IL-8 may induce corneal neovascularization. Computer-assisted analysis of sequential fluorescein angiograms showed that rIL-8 doses ranging from 2 to 40 ng/cornea (P = 0.01), but not high dose rIL-8 (400 ng/cornea), results in neovascularization within 14 days. Repeat fluorescein angiograms 6 weeks after placing angiogenic doses of rIL-8 demonstrated significant regression (P = 0.01) of the vascularity present at 2 weeks, suggesting that IL-8 angiogenesis undergoes dynamic modulation similar to that normally seen in wound healing. To our knowledge, this is the first study showing an angiogenic role for IL-8, a finding that emphasizes the interplay between inflammation and wound healing. Our results imply that corneal-derived IL-8 may be important in corneal neovascularization, in particular, and that IL-8 may modulate wound healing in general. Finally, these results raise the possibility that corneal-derived cytokines, such as IL-8, may obfuscate the effects of agents tested in experimental corneal pocket models.
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              Fundamentals of veterinary ophthalmology


                Author and article information

                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Arquivos Brasileiros de Oftalmologia
                Arq. Bras. Oftalmol.
                Conselho Brasileiro de Oftalmologia (São Paulo, SP, Brazil )
                December 2009
                : 72
                : 6
                : 760-765
                São Carlos SP orgnameUSP orgdiv1Instituto de Química orgdiv2Laboratório de Bioquímica e Biomateriais Brazil
                Araçatuba SP orgnameUNESP orgdiv1Departamento de Apoio, Produção e Sanidade Animal Brazil
                Araçatuba SP orgnameUniversidade Estadual Paulista Brazil
                São Paulo SP orgnameUniversidade de São Paulo Brazil
                Araçatuba SP orgnameUNESP Brazil

                This work is licensed under a Creative Commons Attribution 4.0 International License.

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