Matthias Lueke

Differential expression of vascular endothelial growth factor-a isoforms in neovascular age-related macular degeneration.

Purpose: To investigate the role of vascular endothelial growth factor-A (VEGF-A) isoforms in neovascular age-related macular degeneration. Methods: Choroidal neovascular membranes (CNV) were excised in 24 patients, 8 of them underwent previous photodynamic therapy. All procedures were performed before anti-VEGF therapies were implemented in Germany. Normal human donor eyes served as controls. Messenger RNA expression of total VEGF-A and VEGF-A isoforms was measured. Results: Vascular endothelial growth factor-A121 is the most abundant isoform in CNV and control tissues. In controls, VEGF-A121 is lowest in neural retina and highest in choroids. For total VEGF-A and VEGF-A165, this is vice versa. VEGF-A165 and VEGF-A189 are significantly higher in CNV than in control choroids, the opposite is found for VEGF-A121. After photodynamic therapy, total VEGF-A and VEGF-A121 are increased, VEGF-A165 and VEGF-A189 are decreased. Age-dependently, there is an increase in VEGF-A165 and a decrease in VEGF-A121. Conclusion: Vascular endothelial growth factor-A isoforms are differentially distributed, suggesting that tissue-specific regulation of various isoforms is physiologically important. The disruption of this homeostasis in CNV membranes may be significant in the onset and progression of neovascular age-related macular degeneration. Our findings support the dominant role of VEGF-A121 in neovascular age-related macular degeneration but hint that VEGF-A165 may have an equivalent role in other neovascular retinal pathology.

Comparing the Effects of Two Different Irrigation Solutions on an Isolated Perfused Vertebrate Retina

Purpose: To compare the effect of a taurine-containing intraocular irrigation solution (PuriProtect™) to a standard irrigation solution (BSS™) we evaluated the retinal function using an electroretinogram (ERG) and analyzed the survival of retinal ganglion cells on isolated whole mount retinas. Materials and Methods: During ERG recordings, each irrigation solution was superfused for 45 min with the relevant irrigation solution. To investigate the effects on photoreceptor function, 1 mM asparate was added to obtain a-waves. The recovery of the a- and b-wave was monitored after superfusing the retinas with standard medium again. To evaluate the percentage of dead ganglion cells, retinas were stored for 24 h at 4°C in darkness and after staining the retinas with ethidium homodimer-1 the retinas were analyzed using fluorescence microscopy. Results: The application of standard medium supplemented with 2 mM taurine resulted in a significant increase of the b-wave amplitude compared to standard medium alone. The a-wave amplitudes showed no significant changes under taurine supplementation. Compared to standard medium BSS showed no significant decrease in b-wave amplitudes, but a significant decrease in a-wave amplitudes. In contrast to BSS there were no significant changes in the a- or b-wave amplitudes detectable after the application of PuriProtect. At the end of the washout period no significant changes in a- or b-wave amplitudes were recorded for any tested irrigation solution. Retinas stored for 24 h in PuriProtect or in standard medium with taurine had a statistically significant smaller amount of dead cells than retinas stored in standard medium without taurine supplementation. Conclusions: BSS does not seem to be an ideal irrigation solution, because it compromises the a-wave in the ERG. In contrast to BSS, PuriProtect showed no significant impact on the ERG and showed a better long-term effect on ganglion cell survival. Taurine supplementation, therefore, seems to be neuroprotective and its supplementation to an intraocular irrigation solution favorable for the retina.

Papillary capillary activation in Terson syndrome.

We report the immunopathology and histopathology of a patient with Terson syndrome. The design was an observational case-report. Histopathology and immunohistochemical staining for endoglin (CD105) of an eye from a patient with subarachnoid haemorrhage and Terson syndrome was performed. Immunohistology revealed high papillary endoglin expression. Up-regulation of endoglin indicates activation of endothelial cells. This may suggest a regeneration process after the acute insult.

Current and future strategies for nonexudative age-related macular degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. Recently, the anti-VEGF strategy revolutionized the treatment of the exudative ‘wet’ form of the disease and improved therapeutic outcomes. However, the current strategy does not treat the causative and even more common neurodegenerative ‘dry’ process of the disease. Objectives: In this article we review the current approach and rationale for the present and developing therapeutic strategies that target the nonexudative dry form of AMD. Methods: A review of the literature and ongoing studies was undertaken. Results: Currently, there is no proven drug for the treatment of dry AMD. Cessation of smoking, and nutritional recommendations and supplements are supposed to slow disease progression. Different strategies targeting perfusion, inflammation, oxidative stress and degeneration, or interfering early in – or even prior to – the formation of subretinal pigmented epithelium deposits, may finally succeed in treating the causative processes of the disease. Conclusion: For the nonexudative form of AMD, no established treatment exists, except for the use of oral supplements with high-dose antioxidants that may delay progression. Therefore, a fundamental treatment approach for the neurodegenerative process is needed. Potential future drugs are under development.