Vitamin D protects against oxidative stress and inflammation in human retinal cells

Diabetic retinopathy is a vision-threatening microvascular complication of diabetes and is one of the leading causes of blindness. Oxidative stress and inflammation play a major role in its pathogenesis, and new therapies counteracting these contributors could be of great interest. In the current study, we investigated the role of vitamin D against oxidative stress and inflammation in human retinal pigment epithelium (RPE) and human retinal endothelial cell lines. We demonstrate that vitamin D effectively counteracts the oxidative stress induced by hydrogen peroxide (H2O2). In addition, the increased levels of proinflammatory proteins such as Interleukin (IL)-6, IL-8, Monocyte chemoattractant protein (MCP)-1, Interferon (IFN)-γ, and tumor necrosis factor (TNF)-α triggered by lipopolysaccharide (LPS) exposure were significantly decreased by vitamin D addition. Interestingly, the increased IL-18 only decreased by vitamin D addition in endothelial cells but not in RPE cells, suggesting a main antiangiogenic role under inflammatory conditions. Moreover, H2O2 and LPS induced the alteration and morphological damage of tight junctions in adult retinal pigment epithelium (ARPE-19) cells that were restored under oxidative and inflammatory conditions by the addition of vitamin D to the media. In conclusion, our data suggest that vitamin D could protect the retina by enhancing antioxidant defense and through exhibiting anti-inflammatory properties

A higher proportion of eicosapentaenoic acid (EPA) when combined with docosahexaenoic acid (DHA) in omega-3 dietary supplements provides higher antioxidant effects in human retinal cells

Retinal pigment epithelium (RPE) is a key regulator of retinal function and is directly related to the transport, delivery, and metabolism of long-chain n-3 polyunsaturated fatty acids (n3-PUFA), in the retina. Due to their functions and location, RPE cells are constantly exposed to oxidative stress. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown to have antioxidant effects by different mechanisms. For this reason, we designed an in vitro study to compare 10 formulations of DHA and EPA supplements from different origins and combined in different proportions, evaluating their effect on cell viability, cell proliferation, reactive oxygen species production, and cell migration using ARPE-19 cells. Furthermore, we assessed their ability to rescue RPE cells from the oxidative conditions seen in diabetic retinopathy. Our results showed that the different formulations of n3-PUFAs have a beneficial effect on cell viability and proliferation and are able to restore oxidative induced RPE damage. We observed that the n3-PUFA provided different results alone or combined in the same supplement. When combined, the best results were obtained in formulations that included a higher proportion of EPA than DHA. Moreover, n3-PUFA in the form of ethyl-esters had a worse performance when compared with triglycerides or phospholipid based formulations

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world

Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice

Factores genéticos y ambientales relacionados con el desarrollo de Miopía, Miopía Magna y Maculopatía Miópica en la población española

La miopía es el error refractivo más frecuente a nivel mundial y en las últimas décadas su prevalencia ha ido aumentado de manera exponencial hasta alcanzar casi niveles epidémicos, especialmente entre las generaciones más jóvenes. Este aumento dramático no sólo se ha visto en Asia sino también en Estados Unidos y Europa. Además, se prevé que las tasas de prevalencia tanto de miopía como de miopía magna seguirán aumentando en los próximos años, lo que implica que también aumentarán las complicaciones, como la maculopatía miópica, y la pérdida de visión asociadas a esta patología,. Se ha demostrado que la miopía es una patología multifactorial en la que podrían influir factores tanto genéticos como ambientales y los resultados de este trabajo confirman la importancia de ambos en el desarrollo y progresión de la miopía, miopía magna y maculopatía miópica en población española. Desde el punto de vista genético, los SNPs rs13095226 de COL8A1, y rs634990 de cromosoma 15q14, demostraron tener una asociación con la maculopatía miópica en población española con miopía magna, mientras que factores adicionales como la edad, el sexo, el hábito tabáquico, el historial de embarazos, el error refractivo, la longitud axial (LA) y el estafiloma posterior, también estaban asociados con la maculopatía miópica y la neovascularización coroidea miópica (NVCm) en esta población. Desde el punto de vista ambiental, áreas más pequeñas de autofluorescencia ultravioleta conjuntival (CUVAF), un biomarcador de exposición al aire libre, estaba significativamente asociadas con la miopía en adultos jóvenes, especialmente en los miopes magnos. Tomar el sol sin protección parecía actuar como un factor de confusión en el aumento del área CUVAF en los individuos miopes de la cohorte estudiada, mientras que el uso de gafas no parecía influir en el tamaño del área CUVAF. También se observó una tendencia a pasar menos horas a la semana realizando actividades al aire libre conforme aumentaba el grado de miopía, que fue significativo en los miopes magnos. Además, los participantes con padres miopes tenían más riesgo de desarrollar miopía de inicio temprano y a su vez miopía magna. En conclusión, los resultados de este trabajo respaldan la llamada teoría de la interacción entre genes y medio ambiente como responsable del desarrollo y progresión de la miopía, miopía magna y maculopatía miópica. Según la cual el medio ambiente podría tener un impacto diferencial en el fenotipo de un individuo debido a su genotipo. Es necesario continuar ampliando nuestros conocimiento acerca de los mecanismos fisiopatológicos involucrados en el desarrollo de estas patologías. La capacidad de identificar a los individuos en riesgo nos llevará a plantear nuevas opciones terapéuticas, a un mejor manejo de los pacientes y, en última instancia, a la prevención de las complicaciones y el deterioro visual asociado a esta patología

Factores genéticos y ambientales relacionados con el desarrollo de Miopía, Miopía Magna y Maculopatía Miópica en la población española

La miopía es el error refractivo más frecuente a nivel mundial y en las últimas décadas su prevalencia ha ido aumentado de manera exponencial hasta alcanzar casi niveles epidémicos, especialmente entre las generaciones más jóvenes. Este aumento dramático no sólo se ha visto en Asia sino también en Estados Unidos y Europa. Además, se prevé que las tasas de prevalencia tanto de miopía como de miopía magna seguirán aumentando en los próximos años, lo que implica que también aumentarán las complicaciones, como la maculopatía miópica, y la pérdida de visión asociadas a esta patología,. Se ha demostrado que la miopía es una patología multifactorial en la que podrían influir factores tanto genéticos como ambientales y los resultados de este trabajo confirman la importancia de ambos en el desarrollo y progresión de la miopía, miopía magna y maculopatía miópica en población española. Desde el punto de vista genético, los SNPs rs13095226 de COL8A1, y rs634990 de cromosoma 15q14, demostraron tener una asociación con la maculopatía miópica en población española con miopía magna, mientras que factores adicionales como la edad, el sexo, el hábito tabáquico, el historial de embarazos, el error refractivo, la longitud axial (LA) y el estafiloma posterior, también estaban asociados con la maculopatía miópica y la neovascularización coroidea miópica (NVCm) en esta población. Desde el punto de vista ambiental, áreas más pequeñas de autofluorescencia ultravioleta conjuntival (CUVAF), un biomarcador de exposición al aire libre, estaba significativamente asociadas con la miopía en adultos jóvenes, especialmente en los miopes magnos. Tomar el sol sin protección parecía actuar como un factor de confusión en el aumento del área CUVAF en los individuos miopes de la cohorte estudiada, mientras que el uso de gafas no parecía influir en el tamaño del área CUVAF. También se observó una tendencia a pasar menos horas a la semana realizando actividades al aire libre conforme aumentaba el grado de miopía, que fue significativo en los miopes magnos. Además, los participantes con padres miopes tenían más riesgo de desarrollar miopía de inicio temprano y a su vez miopía magna. En conclusión, los resultados de este trabajo respaldan la llamada teoría de la interacción entre genes y medio ambiente como responsable del desarrollo y progresión de la miopía, miopía magna y maculopatía miópica. Según la cual el medio ambiente podría tener un impacto diferencial en el fenotipo de un individuo debido a su genotipo. Es necesario continuar ampliando nuestros conocimiento acerca de los mecanismos fisiopatológicos involucrados en el desarrollo de estas patologías. La capacidad de identificar a los individuos en riesgo nos llevará a plantear nuevas opciones terapéuticas, a un mejor manejo de los pacientes y, en última instancia, a la prevención de las complicaciones y el deterioro visual asociado a esta patología

Vitamin D protects against oxidative stress and inflammation in human retinal cells

Diabetic retinopathy is a vision-threatening microvascular complication of diabetes and is one of the leading causes of blindness. Oxidative stress and inflammation play a major role in its pathogenesis, and new therapies counteracting these contributors could be of great interest. In the current study, we investigated the role of vitamin D against oxidative stress and inflammation in human retinal pigment epithelium (RPE) and human retinal endothelial cell lines. We demonstrate that vitamin D effectively counteracts the oxidative stress induced by hydrogen peroxide (H2O2). In addition, the increased levels of proinflammatory proteins such as Interleukin (IL)-6, IL-8, Monocyte chemoattractant protein (MCP)-1, Interferon (IFN)-γ, and tumor necrosis factor (TNF)-α triggered by lipopolysaccharide (LPS) exposure were significantly decreased by vitamin D addition. Interestingly, the increased IL-18 only decreased by vitamin D addition in endothelial cells but not in RPE cells, suggesting a main antiangiogenic role under inflammatory conditions. Moreover, H2O2 and LPS induced the alteration and morphological damage of tight junctions in adult retinal pigment epithelium (ARPE-19) cells that were restored under oxidative and inflammatory conditions by the addition of vitamin D to the media. In conclusion, our data suggest that vitamin D could protect the retina by enhancing antioxidant defense and through exhibiting anti-inflammatory properties

Matrix metalloproteinase 13 is associated with age-related choroidal neovascularization

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in older individuals in developed countries. Despite advances in our understanding of AMD, its pathophysiology remains poorly understood. Matrix metalloproteinases (MMPs) have been proposed to play a role in AMD development. In this study, we aimed to characterize MMP-13 in AMD. We used retinal pigment epithelial cells, a murine model of laser-induced choroidal neovascularization, and plasma samples from patients with neovascular AMD to conduct our study. Our results show that MMP13 expression significantly increased under oxidative stress conditions in cultured retinal pigment epithelial cells. In the murine model, MMP13 was overexpressed in both retinal pigment epithelial cells and endothelial cells during choroidal neovascularization. Additionally, the total MMP13 levels in the plasma of patients with neovascular AMD were significantly lower than those in the control group. This suggests a reduced diffusion from the tissues or release from circulating cells in the bloodstream, given that the number and function of monocytes have been reported to be deficient in patients with AMD. Although more studies are needed to elucidate the role of MMP13 in AMD, it could be a promising therapeutic target for treating AMD

A higher proportion of eicosapentaenoic acid (EPA) when combined with docosahexaenoic acid (DHA) in omega-3 dietary supplements provides higher antioxidant effects in human retinal cells

Retinal pigment epithelium (RPE) is a key regulator of retinal function and is directly related to the transport, delivery, and metabolism of long-chain n-3 polyunsaturated fatty acids (n3-PUFA), in the retina. Due to their functions and location, RPE cells are constantly exposed to oxidative stress. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown to have antioxidant effects by different mechanisms. For this reason, we designed an in vitro study to compare 10 formulations of DHA and EPA supplements from different origins and combined in different proportions, evaluating their effect on cell viability, cell proliferation, reactive oxygen species production, and cell migration using ARPE-19 cells. Furthermore, we assessed their ability to rescue RPE cells from the oxidative conditions seen in diabetic retinopathy. Our results showed that the different formulations of n3-PUFAs have a beneficial effect on cell viability and proliferation and are able to restore oxidative induced RPE damage. We observed that the n3-PUFA provided different results alone or combined in the same supplement. When combined, the best results were obtained in formulations that included a higher proportion of EPA than DHA. Moreover, n3-PUFA in the form of ethyl-esters had a worse performance when compared with triglycerides or phospholipid based formulations

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world

Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. Methods: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. Results: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice