Plasma GDF-15 concentration is not elevated in open-angle glaucoma.

AIM: Recently, the level of growth differentiation factor 15 (GDF-15) in blood, was proposed as biomarker to detect mitochondrial dysfunction. In the current study, we evaluate this biomarker in open-angle glaucoma (OAG), as there is increasing evidence that mitochondrial dysfunction plays a role in the pathophysiology of this disease. METHODS: Plasma GDF-15 concentrations were measured with ELISA in 200 OAG patients and 61 age-matched controls (cataract without glaucoma). The OAG patient group consisted of high tension glaucoma (HTG; n = 162) and normal tension glaucoma (NTG; n = 38). Groups were compared using the Kruskal-Wallis nonparametric test with Dunn's multiple comparison post-hoc correction. GDF-15 concentration was corrected for confounders identified with forward linear regression models. RESULTS: Before correcting for confounders, median plasma GDF-15 levels was significantly lower in the combined OAG group (p = 0.04), but not when analysing HTG and NTG patients separately. Forward linear regression analysis showed that age, gender, smoking and systemic hypertension were significant confounders affecting GDF-15 levels. After correction for these confounders, GDF-15 levels in OAG patients were no longer significantly different from controls. Subgroup analysis of the glaucoma patients did not show a correlation between disease severity and plasma GDF-15, but did reveal that for NTG patients, intake of dietary supplements, which potentially improve mitochondrial function, correlated with lower plasma GDF-15. CONCLUSION: The present study suggests that plasma GDF-15 is not suited as biomarker of mitochondrial dysfunction in OAG patients.

Modeling the Mechanical Parameters of Glaucoma.

Glaucoma is a major eye disease characterized by a progressive loss of retinal ganglion cells (RGCs). Biomechanical forces as a result of hydrostatic pressure and strain play a role in this disease. Decreasing intraocular pressure is the only available therapy so far, but is not always effective and does not prevent blindness in many cases. There is a need for drugs that protect RGCs from dying in glaucoma; to develop these, we need valid glaucoma and drug screening models. Since in vivo models are unsuitable for screening purposes, we focus on in vitro and ex vivo models in this review. Many groups have studied pressure and strain model systems to mimic glaucoma, to investigate the molecular and cellular events leading to mechanically induced RGC death. Therefore, the focus of this review is on the different mechanical model systems used to mimic the biomechanical forces in glaucoma. Most models use either cell or tissue strain, or fluid- or gas-controlled hydrostatic pressure application and apply it to the relevant cell types such as trabecular meshwork cells, optic nerve head astrocytes, and RGCs, but also to entire eyes. New model systems are warranted to study concepts and test experimental compounds for the development of new drugs to protect vision in glaucoma patients. Impact Statement The outcome of currently developed models to investigate mechanically induced retinal ganglion cell death by applying different mechanical strains varies widely. This suggests that a robust glaucoma model has not been developed yet. However, a comprehensive overview of current developments is not available. In this review, we have therefore assessed what has been done before and summarized the available knowledge in the field, which can be used to develop improved models for glaucoma research.

Monitoring neovascularization in aggressive posterior retinopathy of prematurity using optical coherence tomography angiography.

We describe the use of optical coherence tomography angiography (OCTA) in detecting and monitoring regression of the neovascular complex (NVC) in a case of aggressive posterior retinopathy of prematurity (AP-ROP). A premature Asian Indian girl with AP-ROP underwent laser photoablation at 26 days of life. Persistent NVC at the posterior border of the lasered retinal bed was detected clinically. On en face spectral domain optical coherence tomography (SD-OCT) and OCTA, the NVC appeared as an arborizing vascular net in the superficial capillary plexus. The deep capillary plexus and outer retinal layers showed corresponding flow outlines that suggested deeper extensions of the lesion. Supplemental laser treatment of the NVC was performed. Ten days later repeat en face SD-OCT and OCTA of the identical retinal location revealed that the vascular tortuosity and dilatation had reduced and that the flow lesions in the deeper layers were undetectable. Our findings in this case suggest that the NVC in AP-ROP extends beyond the superficial retina.

Lutein and Factor D: two intriguing players in the field of age-related macular degeneration.

Age-related macular degeneration (AMD) is a progressive eye disease that impairs central vision among elderly populations in Western, industrialized countries. In this review we will focus on the role of factor D (FD) and lutein in AMD. FD is a rate-limiting enzyme of the alternative complement activation pathway that may play an important role in the development of AMD. Several independent studies have shown a significant increase in the level of a number of complement factors of the alternative pathway, including factor D in the blood of AMD patients as compared to healthy individuals, which suggests a systemic involvement in the pathogenesis of AMD. FD, also called adipsin, is mainly produced by adipose tissue. Besides playing a role in the activation of the alternative pathway, FD is also known to regulate the immune system. Of interest is our preliminary finding that lutein supplementation of early AMD cases was shown to lower the level of systemic FD. If confirmed, these findings provide further support for the application of anti-factor D intervention as a new approach to control the development of this disease.