10 research outputs found
Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light
AbstractMitochondria produce adenosine triphosphate (ATP), critical for cellular metabolism. ATP declines with age, which is associated with inflammation. Here, we measure retinal and brain ATP in normal C57BL/6 and complement factor H knockout mice (Cfhâ/â), which are proposed as a model of age-related macular degeneration. We show a significant premature 30% decline in retinal ATP in Cfhâ/â mice and a subsequent shift in expression of a heat shock protein that is predominantly mitochondrial (Hsp60). Changes in Hsp60 are associated with stress and neuroprotection. We find no differences in brain ATP between C57BL/6 and Cfhâ/â mice. Near infrared (NIR) increases ATP and reduces inflammation. ATP decline in Cfhâ/â mice was corrected with NIR which also shifted Hsp60 labeling patterns. ATP decline in Cfhâ/â mice occurs before inflammation becomes established and photoreceptor loss occurs and may relate to disease etiology. However, ATP levels were corrected with NIR. In summary, we provide evidence for a mitochondrial basis for this disease in mice and correct this with simple light exposure known to improve mitochondrial function
Maternal Toxoplasma gondii infection affects proliferation, differentiation and cell cycle regulation of retinal neural progenitor cells in mouse embryo
BackgroundToxoplasmosis affects one third of the world population and has the protozoan Toxoplasma gondii as etiological agent. Congenital toxoplasmosis (CT) can cause severe damage to the fetus, including miscarriages, intracranial calcification, hydrocephalus and retinochoroiditis. Severity of CT depends on the gestational period in which infection occurs, and alterations at the cellular level during retinal development have been reported. In this study, we proposed a mouse CT model to investigate the impact of infection on retinal development.MethodsPregnant females of pigmented C57BL/6 strain mice were infected intragastrically with two T. gondii cysts (ME49 strain) at embryonic day 10 (E10), and the offspring were analyzed at E18.ResultsInfected embryos had significantly smaller body sizes and weights than the PBS-treated controls, indicating that embryonic development was affected. In the retina, a significant increase in the number of Ki-67-positive cells (marker of proliferating cells) was found in the apical region of the NBL of infected mice compared to the control. Supporting this, cell cycle proteins Cyclin D3, Cdk6 and pChK2 were significantly altered in infected retinas. Interestingly, the immunohistochemical analysis showed a significant increase in the population of ÎČ-III-tubulin-positive cells, one of the earliest markers of neuronal differentiation.ConclusionsOur data suggests that CT affects cell cycle progression in retinal progenitor cells, possibly inducing the arrest of these cells at G2/M phase. Such alterations could influence the differentiation, anticipating/increasing neuronal maturation, and therefore leading to abnormal retinal formation. Our model mimics important events observed in ocular CT
Immunohistochemical characterization of NMDA, kainic acid and aspartate-induced released of GABA in chick retina
Immunohistochemical characterization of NMDA, kainic acid and aspartate-induced released of GABA in chick retina
Contribution of MĂŒller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation
Diabetic retinopathy is a neurovascular complication of diabetes and the main cause of vision loss in adults. Glial cells have a key role in maintenance of central nervous system homeostasis. In the retina, the predominant element is the MĂŒller cell, a specialized cell with radial morphology that spans all retinal layers and influences the function of the entire retinal circuitry. MĂŒller cells provide metabolic support, regulation of extracellular composition, synaptic activity control, structural organization of the bloodâretina barrier, antioxidant activity, and trophic support, among other roles. Therefore, impairments of MĂŒller actions lead to retinal malfunctions. Accordingly, increasing evidence indicates that MĂŒller cells are affected in diabetic retinopathy and may contribute to the severity of the disease. Here, we will survey recently described alterations in MĂŒller cell functions and cellular events that contribute to diabetic retinopathy, especially related to oxidative stress and inflammation. This review sheds light on MĂŒller cells as potential therapeutic targets of this disease
Contribution of Müller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation
Diabetic retinopathy is a neurovascular complication of diabetes and the main cause of vision loss in adults. Glial cells have a key role in maintenance of central nervous system homeostasis. In the retina, the predominant element is the Müller cell, a specialized cell with radial morphology that spans all retinal layers and influences the function of the entire retinal circuitry. Müller cells provide metabolic support, regulation of extracellular composition, synaptic activity control, structural organization of the blood–retina barrier, antioxidant activity, and trophic support, among other roles. Therefore, impairments of Müller actions lead to retinal malfunctions. Accordingly, increasing evidence indicates that Müller cells are affected in diabetic retinopathy and may contribute to the severity of the disease. Here, we will survey recently described alterations in Müller cell functions and cellular events that contribute to diabetic retinopathy, especially related to oxidative stress and inflammation. This review sheds light on Müller cells as potential therapeutic targets of this disease