Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress.

Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661 W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661 W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.

Single-string, closed-loop fixation modification to reposit a dislocated triple-looped haptic intraocular lens.

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed.

Effect of nintedanib thermo-sensitive hydrogel on neovascularization in alkali burn rat model.

AIM: To investigate the effects of nintedanib thermo-sensitive hydrogel (NTH) on neovascularization and related markers in corneal alkali burns of Wistar rats. METHODS: NTH was prepared by grinding, and its phase-transition temperature was determined. Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups (n=10, each): model group treated with 0.9% saline once a day, NTH group with 0.2% nintedanib b.i.d, and dexamethasone group with dexamethasone ointment once a day. The left eye of rats served as the controls. The corneal transparency was observed under a slit-lamp microscope, and the area of neovascularization was calculated. On day 7, the rats were sacrificed, and the cornea was removed and embedded with paraffin, then stained with hematoxylin-eosin, and the expression of vascular endothelial growth factor receptor 2 (VEGFR-2) and CD31 in the corneal tissues of each group was detected by immunofluorescence. RESULTS: The phase-transition temperature of nintedanib obtained by grinding was 37°C after adding artificial tears. The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group, and the neovascularization area was significantly smaller than that in the model group (P<0.05). Moreover, CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group. CONCLUSION: NTH becomes colloidal at body temperature, which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.

Mitochondrial transfer RNA variants and primary congenital glaucoma.

Variants in mitochondrial DNA (mtDNA) are the most important causes for vision loss, the mt-tRNA variants being the largest group among them. In this study, we report the molecular characterization of 15 mt-tRNA variants with primary congenital glaucoma (PCG). Based on phylogenetic approach, we found that only half of them were definitely pathogenic with PCG, other mutations were single nucleotide polymorphisms (SNP) in human population. Thus, our study provided novel insight into the pathogenesis of PCG.

Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A.

Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment.