Experimental vitreoretinal surgery in the rabbit eye - electrophysiology and morphology

Sammanfattning: The field of vitreoretinal surgery has expanded greatly over the last decades. A continuous refinement of surgical methods and instruments has increased the number of treatable retinal disorders. Vitrectomy, retinectomy and laser treatment are all part of the modern surgical arsenal. In order to further develop and refine these methods, and also to improve the knowledge of the mechanisms behind their efficiency, standardized animal models including functional and histological evaluations are of great value. Full-field electroretinography (ERG) and multifocal electroretinography (mfERG) are methods by which electrical activity from neurons in the retina can be measured. ERG measures the total response of cones and/or rods after light stimulation whereas mfERG measures the focal cone-mediated activity from the central part of the retina. In this thesis the ERG and mfERG protocols were adapted and standardized for the rabbit eye. Reliable and reproducible ERG readings were obtained, and combining the technique with immunohistochemistry, the retinal impact of various surgical procedures in the rabbit eye was studied. After vitrectomy, ERG recordings displayed reduced amplitudes up to 4 weeks postoperatively, with rods more affected than cones. A general glial fibrillary acidic protein (GFAP) labeling throughout the retina was noted postoperatively, with a more intense labeling in eyes where a low cutting rate of the vitrectomy instrument had been used, implying a higher degree of traumatic impact compared with high-speed settings. An experimental method was also developed for performing a retinectomy in the rabbit eye, where a part of the retina was surgically removed. Using the mfERG, it was shown that the procedure induces a general reduction of the central retinal function for 1 month. After this time, retinal function was gradually restored except for in the area of removed retina. The study thus showed that lesions down to 1 mm in diameter could be detected by the method. In the last 2 studies, focal laser photocoagulation was performed in the rabbit retina. ERG measurements did not indicate a reduction in function, but in the mfERG, the implicit time was slightly delayed implying a local reduction in function. The GFAP labeling was intense in the entire retina in the immediate postoperative phase, and the protein kinase C (PKC) labeling displayed a previously not known pattern with an activation followed by a depletion of the protein expression. The altered PKC expression could be a part of the explanation of the efficiency of laser treatment in diabetic retinopathy. Our findings indicate that focal laser treatment induces a general retinal response evident by alterations in the expression of several important proteins. However, retinal function is not negatively compromised, and we conclude that the treatment at least in the short term is safe.