PURPOSE To assess the histopathological changes in a postmortem sample derived from an eye donor with Macular Telangiectasia Type 2 (MacTel type 2) to gain further insight into the cause of the disease. DESIGN Clinicopathological case report PARTICIPANTS Postmortem tissue was collected from 5 different donors: one MacTel type 2 patient, one healthy control, two type 2 diabetic patients; one with retinopathy and one without retinopathy, and one patient with unilateral Coat’s disease. METHODS Macular pigment distribution in the posterior part of freshly dissected eyes was documented by macro photography. Paraffin sections from both the macular and peripheral regions were assessed using antigen retrieval and immunohistochemistry to study the distribution of cell-specific markers. Blood vessels were visualized with antibodies directed against collagen IV and claudin5, glial cells with antibodies against glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase (GS) and retinaldehyde binding protein (RLBP1, also known as CRALBP), microglia with an antibody against allograft inflammatory factor 1 (AIF1, also known as Iba1) and photoreceptors with antibodies against rhodopsin and opsin. Using anatomical landmarks the sections were then matched with the macular pigment distribution and a fluorescein angiogram of the patient that was taken before the patient’s death. MAIN OUTCOME MEASURES Presence and distribution of macular pigment and cell-specific markers. RESULTS Macular pigment was absent in the macula. Furthermore, abnormally dilated capillaries were identified in a macular region that correlated spatially with regions of fluorescein leakage in an angiogram that was taken 12 years prior to death. These telangiectatic vessels displayed a marked reduction of the basement membrane component collagen IV, indicating vascular pathology. GFAP was limited to retinal astrocytes and no reactive Müller cells were identified. Importantly, reduced immunoreactivity with Müller cell markers (vimentin, GS and RLBP1) in the macula was observed. The area that lacked Müller cells corresponded with the region of depleted macular pigment. CONCLUSIONS These findings suggest that macular Müller cell loss or dysfunction is a critical component of MacTel type 2, which may have implications for future treatment strategies.

No abstract

The purpose of this study was to describe the ultrastructural features of an in vitro capillary endothelial cell model of blood-retinal barrier permeability and to relate morphological features with transendothelial electrical resistance. The electrical resistance of endothelial cell monocultures on small and large pore size polycarbonate Transwell filters was measured and compared with cocultures of endothelial cells and Müller cells. There was a wide variation in electrical resistance measurements with many preparations not achieving a functional barrier. The ultrastructural features associated with barrier function in vitro were studied by comparing cultures that exhibited a 'tight' or 'leaky' barrier when measured immediately prior to processing for electron microscopy. Preparations with low transendothelial electrical resistance were associated with irregular cell growth when studied morphologically. It was concluded that parallel light and electron microscopic studies are important for validation of in vitro models of vascular endothelial permeability.

Aim: To investigate the in vitro effect of laser photocoagulation on blood-retinal barrier permeability. Methods: Retinal capillary endothelial cells were exposed to supernatants from long term co-cultured cells that were argon laser treated. Endothelial cell permeability was analysed by (1) measurement of transendothelial electrical resistance and (2) Results: Laser photocoagulation of various retinal cells and control ECV304 cells in the lower chamber did not appreciably improve permeability of the endothelial cell monolayer compared with that of unlasered cells. However, medium that was conditioned by mixed retinal pigmented epithelium and Müller cells significantly reduced both inulin (43.2% (SD 6.5%) equilibration in mixed cultures v 59.8% (SD 7.0%) control cells, p,0.05) and albumin (15.1% (SD 3.8%) v 31.1% (SD 6.7%), p,0.05) permeability of the endothelial cell monolayers. A fourfold increase in transendothelial electrical resistance was also seen. Conclusions: These results are consistent with the hypothesis that interaction of Müller cells with retinal pigmented epithelium induced by laser treatment results in secretion of soluble factor(s), which reduces permeability of retinal vascular endothelium. Identification of these factor(s) may have implications for the clinical treatment of macular oedema secondary to diabetic retinopathy and other diseases.