All-trans retinoic acid regulates the expression of MMP-2 and TGF-ß2 via RDH5 in retinal pigment epithelium cells.

AIM: To investigate the effect of all-trans retinoic acid (ATRA) on retinol dehydrogenase 5 (RDH5), matrix metalloproteinase-2 (MMP-2) and transforming growth factor-ß2 (TGF-ß2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-ß2 in retinal pigment epithelium (RPE) cells. METHODS: After adult RPE cell line-19 (ARPE-19 cells) intervened with gradient concentrations of ATRA (0-20 µmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect RDH5, MMP-2 and TGF-ß2 mRNA expression. Then, after ARPE-19 cells transfected with three different siRNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-ß2 mRNA within them was detected by qRT-PCR. RESULTS: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 µmol/L and compared with the normal control group (P=0.027 and P=0.031, respectively). qRT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 mRNA (P<0.001) and promote the expression of MMP-2 and TGF-ß2 mRNA (P=0.03 and P<0.001, respectively) in a dose-dependent manner, especially when treated with 5 µmol/L ATRA. The knockdown efficiency of RDH5 siRNA varies with different targets, among which RDH5 siRNA-435 had the highest knockdown efficiency, i.e., more than 50% lower than that of the negative control group (P=0.02). When RDH5 was knocked down for 48h, the results of qRT-PCR showed that the expressions of MMP-2 and TGF-ß2 mRNA were significantly up-regulated (P<0.001). CONCLUSION: ATRA inhibits the expression of RDH5 and promotes MMP-2 and TGF-ß2, and further RDH5 knockdown significantly upregulates MMP-2 and TGF-ß2. These findings suggest that RDH5 may be involved in an epithelial-mesenchymal transition of RPE cells mediated by ATRA.

Expression of SCO1 and SCO2 after form-deprivation myopia in Guinea pigs.

PURPOSE: The retina is a highly energy-consuming tissue associated with visual development, and the reduced quality of retinal imaging can be related to myopia. Synthesis of cytochrome c oxidase 1 (SCO1) and synthesis of cytochrome c oxidase 2 (SCO2) are involved in ATP (adenosine triphosphate) synthesis and energy metabolism. This study aimed to observe the morphologic changes and investigate the expression of SCO1 and SCO2 induced by form-deprivation myopia (FDM) in the retina and sclera of guinea pigs. METHODS: Thirty-six 3-week-old male guinea pigs were randomly assigned to one of two groups: (1) the model group (n = 18), in which the right eyes were covered by a thin opaque balloon as FDM group, and the left eyes were uncovered and served as the contralateral control group; (2) the blank control group (n = 18), in which bilateral eye received no manipulation. Eyeballs were enucleated for histological analysis. The retina and sclera of the guinea pigs were separated to determine the protein and mRNA expression levels of SCO1 and SCO2, respectively. RESULTS: After four weeks of form deprivation (FD), the refractive degree and axial length increased significantly (P < 0.001). The retinal and scleral tissues were moderately thinner, and the ganglion cells and the cells of inner and outer nuclear layers in the retina became fewer. Compared with the contralateral control group (P < 0.001) and the blank control group (P < 0.001), the collagen content of the sclera became less in the FDM group. The protein and mRNA expression levels of SCO1 and SCO2 in the FDM group were significantly lower than those in the contralateral control group and the blank control group (P < 0.05). CONCLUSIONS: The morphologies of the retina and sclera were changed, and the expression of SCO1 and SCO2 at the protein and transcription levels was significantly reduced in the FDM group. Given these changes, SCO1 and SCO2 genes may be involved in myopic progression.

Ocular Characteristics of Patients with Leber Congenital Amaurosis 6 Caused by Pathogenic RPGRIP1 Gene Variation in a Chinese Cohort.

PURPOSE: To delineate the clinical and genetic characteristics of Chinese patients with RPGRIP1-associated Leber congenital amaurosis 6 (LCA6). METHODS: After screening 352 unrelated families with clinically diagnosed RP, five LCA6 patients with RPGRIP1 variations from unrelated Chinese families were identified. Full ophthalmology examinations, including decimal best-corrected visual acuity (BCVA), fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), multifocal electroretinography (mfERG), perimetry, and flash visual evoked potential (FVEP), were performed. Target next-generation sequencing (NGS) and Sanger sequencing were performed for the five patients to identify and to validate candidate disease-causing variants. RESULTS: Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect, at an early age. Interestingly, LCA6 exhibited extensive clinical heterogeneity and the changes in the morphology and function were not completely consistent in the five LCA6 patients. Case 1 showed extensive inferior-nasal retinal atrophy with a corresponding area of hypofluorescence in fundus autofluorescence, and the fundus photograph was nearly normal in cases 2 and 3. The ERG results displayed a moderately reduced rod-system response in cases 1 and 2 and a significant reduced rod-system response in case 3. Both case 4 and case 5 showed mottled pigmentation in fundi and an unrecordable rod and cone-system response in ERG. Moreover, we identified eight compound variants and one homozygous variant in the five patients with RPGRIP1. CONCLUSIONS: This is the largest report focused on the clinical electrophysiological features of patients with associated LCA6 caused by the variation in the RPGRIP1 gene in the Chinese population with an enriched phenotypic and genotypic background of LCA6 to improve future gene therapies.

Amino acid-templated zinc phosphites: low-dimensional structures, fluorescence, and nonlinear optical properties.

Two new zinc phosphites were prepared using the amino acid alanine as a structure-directing agent. They have tubular and ladder-like structures, exhibiting blue fluorescence upon UV light irradiation. Notably, the tubular structure is unprecedented in metal phosphite systems. The compound is a nonlinear optically active solid with a second-harmonic generation efficiency of about 1.2 times that of KH2PO4 (KDP).

The common YAP activation mediates corneal epithelial regeneration and repair with different-sized wounds.

Regeneration/repair after injury can be endowed by adult stem cells (ASCs) or lineage restricted and even terminally differentiated cells. In corneal epithelium, regeneration after a large wound depends on ASCs (limbal epithelial stem cells, LESCs), whereas repair after a small wound is LESCs-independent. Here, using rat corneal epithelial wounds with different sizes, we show that YAP activation promotes the activation and expansion of LESCs after a large wound, as well as the reprogramming of local epithelial cells (repairing epithelial cells) after a small wound, which contributes to LESCs-dependent and -independent wound healing, respectively. Mechanically, we highlight that the reciprocal regulation of YAP activity and the assembly of cell junction and cortical F-actin cytoskeleton accelerates corneal epithelial healing with different-sized wounds. Together, the common YAP activation and the underlying regulatory mechanism are harnessed by LESCs and lineage-restricted epithelial cells to cope with corneal epithelial wounds with different sizes.

Pillared-layered indium phosphites templated by amino acids: isoreticular structures, water stability, and fluorescence.

Two crystalline open-framework indium phosphites (denoted SCU-31 and SCU-32) were prepared using amino acids as structure-directing agents. They have isoreticular pillared-layered structures built up from 6 × 1 and 4 = 1 clusters. Notably, the two compounds show excellent water stability and exhibit blue fluorescence under UV light irradiation at room temperature. The proton-conducting behaviour of SCU-31 was also investigated.

Remediation of saline-sodic soil with flue gas desulfurization gypsum in a reclaimed tidal flat of southeast China.

Salinization and sodicity are obstacles for vegetation reconstruction of coastal tidal flat soils. A study was conducted with flue gas desulfurization (FGD)-gypsum applied at rates of 0, 15, 30, 45 and 60Mg/ha to remediate tidal flat soils of the Yangtze River estuary. Exchangeable sodium percentage (ESP), exchangeable sodium (ExNa), pH, soluble salt concentration, and composition of soluble salts were measured in 10cm increments from the surface to 30cm depth after 6 and 18months. The results indicated that the effect of FGD-gypsum is greatest in the 0-10cm mixing soil layer and 60Mg/ha was the optimal rate that can reduce the ESP to below 6% and decrease soil pH to neutral (7.0). The improvement effect was reached after 6months, and remained after 18months. The composition of soluble salts was transformed from sodic salt ions mainly containing Na(+), HCO3(-)+CO3(2-) and Cl(-) to neutral salt ions mainly containing Ca(2+) and SO4(2-). Non-halophyte plants were survived at 90%. The study demonstrates that the use of FGD-gypsum for remediating tidal flat soils is promising.