P-aminobenzoic acid promotes retinal regeneration through activation of Ascl1a in zebrafish

The retina of zebrafish can regenerate completely after injury.M ultiple studies have demonstrated that metabolic alte rations occur during retinal damage;however to date no study has identified a link between metabolites and retinal regeneration of zebrafish.Here,we performed an unbiased metabolome sequencing in the N-methyl-D-aspartic acid-damaged retinas of zebrafish to demonstrate the metabolomic mechanism of retinal regeneration.Among the differentially-ex pressed metabolites,we found a significant decrease in p-aminobenzoic acid in the N-methyl-D-aspartic acid-damaged retinas of zebrafish.Then,we investigated the role of p-aminobenzoic acid in retinal regeneration in adult zebrafish.Impo rtantly,p-aminobenzoic acid activated Achaetescute complex-like 1a expression,thereby promoting Müller glia reprogramming and division,as well as Müller glia-derived progenitor cell proliferation.Finally,we eliminated folic acid and inflammation as downstream effectors of PABA and demonstrated that PABA had little effect on Müller glia distribution.Taken together,these findings show that PABA contributes to retinal regeneration through activation of Achaetescute complex-like 1a expression in the N-methyl-Daspartic acid-damaged retinas of zebrafish.

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

Clinical efficacy of the partial rectus muscle transportation procedure for paralytic strabismus

AIM:To analyze the clinical efficacy of the partial rectus muscle transportation(PRT)procedure for paralytic strabismus due to single rectus muscle palsy.METHODS:In total,28 patients(31 eyes)who underwent the PRT procedure for paralytic strabismus due to single rectus muscle palsy were retrospectively examined.The following data were collected pre-and postoperatively:angle of deviation in the primary position,presence of diplopia in the primary position,presence of compensatory head posture,and motility of the affected eye.The follow-up period was 6 mo.RESULTS:Based on the preoperative and intraoperative findings,different operations were performed:2 eyes were treated with PRT,26 eyes were treated with PRT combined with the recession of the antagonist muscle(Am)of the paralytic rectus muscle,and 3 eyes were treated with PRT along with the recession of the Am and the yoke muscle(Ym).On the first day after the operation,24 patients were found to be orthophoric in the primary position,without diplopia or abnormal head posture.Moreover,2 patients with monocular lateral rectus muscle palsy had mild overcorrection to 5 prism diopters(PD)and 8 PD,respectively,whereas 2 patients with binocular lateral rectus muscle palsy had mild undercorrection to 8 PD and 10 PD,respectively.During the 6-month follow-up period,the mean deviation was rectified from 96.79±41.21 PD to 0.64±2.38 PD(t=12.48,P<0.001),whereas the deviations in the 2 patients with mild overcorrection were corrected to orthotropia.The mean preoperative limitation of motility improved from-4.55±0.51 to-2.65±0.61(t=-15.13,P<0.001)after 6 mo postoperatively.CONCLUSION:PRT is an effective treatment for complete paralytic strabismus due to single rectus muscle palsy,and can achieve stable clinical efficacy.

Anti-scarring effect of sodium hyaluronate at filtration pathway after filtering surgery in rabbits

AIM: To investigate the anti-scarring effect of sodium hyaluronate(HA) at filtration pathway after filtering surgery in a rabbit model.METHODS: Fifteen healthy adult New Zealand white rabbits were selected for trabeculectomy in both eyes. The right eyes were used as HA group with 0.1 m L HA injected into the anterior chamber at the end of the operation;the left eyes were used with 0.1 m L sodium lactate Ringer’s solution(RS) injected into the anterior chamber as RS group. Intraocular pressure(IOP), filtering blebs morphology, inflammatory reaction and complications were observed at the 7, 60, and 90 d after surgery.RESULTS: One day after surgery, the IOP of HA and RS groups were 12.75±1.92 and 10.50±1.59 mm Hg(P=0.005). At the 7;day postoperative, the filtering blebs of each group were functional type and TGF-β expression was significantly difference in both groups(0.10±0.01 vs 0.14±0.02, P=0.024). After 60 d of the operation, all filtering blebs were scarring and alpha-smooth muscle actin(α-SMA) expression was significantly difference in both groups(0.40±0.04 vs 0.35±0.02, P=0.032). α-SMA positive cells were mainly distributed in the junction of conjunctiva and sclera and around the blood vessels. The collagen volume fraction(CVF) of HA and RS group was(75.49±7.01)% and(79.93±5.35)%(P=0.044). On the 90;day after the operation, CVF was(82.57±5.19)% and(88.08±1.75)% in HA and RS groups(P=0.036). There was no α-SMA positive cell in HA group, while a few positive cells were observed in RS group(P=0.000).CONCLUSION: HA has effect of anti-scar and antiinflammation on filtration pathway after filtering surgery within 3 mo by inhibiting fibroblast proliferation and collagen deposition.

Congenital fibrovascular pupillary membranes: case series with pathological correlation and surgical treatment

Dear Editor,We present three cases of congenital fibrovascular pupillary membranes(CFPM) with pathological correlation and surgical treatment. CFPM was first described by Cibis et al;as a new entity of anterior segment malformation termed “congenital pupillary-iris-lens membrane with goniodysgenesis”.

Endoplasmic reticulum stress: molecular mechanism and therapeutic targets

The endoplasmic reticulum(ER)functions as a quality-control organelle for protein homeostasis,or"proteostasis".The protein quality control systems involve ER-associated degradation,protein chaperons,and autophagy.