Regulation of proton-coupled folate transporter in retinal Müller cells by the antipsoriatic drug monomethylfumarate.

Fumaric acid esters are used to treat psoriasis, an inflammatory skin disease characterized by keratinocyte proliferation. Inflammation and proliferation are hallmarks of retinal disease; hence, fumaric acid esters may have therapeutic value in retinal pathology. In diseased retinas, Müller glial cells (MCs) undergo reactive gliosis, a hyperproliferative state.

Homocysteine-mediated modulation of mitochondrial dynamics in retinal ganglion cells.

Purpose: To evaluate the effect of excess homocysteine on the regulation of retinal ganglion cell mitochondrial dynamics.

Methods: Mice deficient in cystathionine-β-synthase (cbs) were used as a model of hyperhomocysteinemia. Gene and protein expression analyses of Opa1 and Fis1 were performed on cbs⁺/⁻ neural retinas.

Cyclic 3',5'-guanosine monophosphate-dependent protein kinase inhibits colon cancer cell adaptation to hypoxia.

Background: Type 1 cyclic 3',5'-guanosine monophosphate-dependent protein kinase (PKG) has recently been reported to inhibit tumor growth and angiogenesis. These effects suggest that PKG activation may have therapeutic value for colon cancer treatment, but the signaling downstream of this enzyme is poorly understood. The present study examined the mechanism underlying the inhibition of angiogenesis by PKG.

The role of N-methyl-D-aspartate receptor activation in homocysteine-induced death of retinal ganglion cells.

Purpose: Elevated plasma homocysteine has been implicated in glaucoma, a vision disorder characterized by retinal ganglion cell death. The toxic potential of homocysteine to ganglion cells is known, but the mechanisms are not clear. A mechanism of homocysteine-induced death of cerebral neurons is via N-methyl-D-aspartate (NMDA) receptor overstimulation, leading to excess calcium influx and oxidative stress.

Molecular and biochemical characterization of folate transport proteins in retinal Müller cells.

Purpose: To analyze the mechanisms of folate uptake in retinal Müller cells.

Methods: RT-PCR and Western blot analysis were performed in freshly isolated neural retina and RPE/eyecup, primary mouse Müller cells, and rMC-1 cells for the three known folate transport proteins folate receptor alpha (FRalpha), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC). Laser scanning confocal microscopy (LSCM) and immunoelectron microscopy were used to determine the subcellular location of FRalpha and PCFT in primary Müller cells.

Sensitivity of staurosporine-induced differentiated RGC-5 cells to homocysteine.

Purpose: Homocysteine is implicated in ganglion cell death associated with glaucoma. To understand mechanisms of homocysteine-induced cell death, we analyzed the sensitivity of the RGC-5 cell line, differentiated using staurosporine, to physiologically-relevant levels of the excitotoxic amino acid homocysteine.

Methods: RGC-5 cells were differentiated 24 hr using 316 nM staurosporine and tested for expression of Thy 1.