Road dust exposure and human corneal damage in a plateau high geological background provincial capital city: Spatial distribution, sources, bioaccessibility, and cytotoxicity of dust heavy metals.

Ocular surface diseases are common in the plateau city, Kunming China, the continued daily exposure to heavy metals in dust may be an important inducement. In this study, the 150 road dust samples from five functional areas in Kunming were collected. The concentrations, distribution, possible sources, and bioaccessibility of heavy metals were analyzed. The adverse effects of dust extracts on human corneal epithelial cells and the underlying mechanisms were also assessed. The concentrations (mg·kg-1) of As (19.1), Cd (2.67), Cr (90.5), Cu (123), Pb (78.4), and Zn (389) in road dust were higher than the soil background, with commercial and residential areas showing the highest pollution. Their bioaccessibility in artificial tears was As (6.59 %) > Cu (5.11 %) > Ni (1.47 %) > Cr (1.17 %) > Mn (0.84 %) > Cd (0.76 %) > Zn (0.50 %) > Pb (0.31 %). The two main sources of heavy metals included tire and mechanical abrasion (24.5 %) and traffic exhaust (21.6 %). All dust extracts induced cytotoxicity, evidenced by stronger inhibition of cell viability, higher production of ROS, and altered mRNA expression of antioxidant enzymes and cell cycle-related genes, with commercial- areas-2 (CA2)-dust extract showing the greatest oxidative damage and cell cycle arrest. Our data may provide new evidence that dust exposure in high geological background cities could trigger human cornea damage.

Causal effects of serum lipid biomarkers on early age-related macular degeneration using Mendelian randomization.

BACKGROUND: Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear. METHODS: In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110). RESULTS: MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10-8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10-6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71-0.84, P = 5.02 × 10-10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results. CONCLUSION: This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

Effects of TCPP and TCEP exposure on human corneal epithelial cells: Oxidative damage, cell cycle arrest, and pyroptosis.

Tris(2-chloroisopropyl) phosphate (TCPP) and Tris(2-chloroethyl) phosphate (TCEP) are the widely used organophosphorus flame retardants indoors and easily accessible to the eyes as the common adhesive components of dust and particle matter, however, hardly any evidence has demonstrated their corneal toxicity. In this study, the adverse effects of TCPP, TCEP, and TCPP + TCEP exposure on human corneal epithelial cells (HCECs) were investigated. The cell viability and morphology, intracellular reactive oxygen species (ROS), cell cycle, and the expressions of cell cycle and pyroptosis-related genes were assessed to explain the underlying mechanisms. Compared to individual exposure, co-exposure to TCPP20+TCEP20 showed higher cytotoxicity with a sharp decrease of >30% in viability and more serious oxidative damage by increasing ROS production to 110.92% compared to the control group. Furthermore, the cell cycle arrested at the S phase (36.20%) was observed after combined treatment, evidenced by the upregulation of cyclin D1, CDK2, CDK4, CDK6, p21, and p27. Interestingly, pyroptosis-related genes GSDMD, Caspase-1, NLRP3, IL-1ß, IL-18, NLRP1, and NLRC4 expressions were promoted with cell swelling and glowing morphology. Oxidative stress and cell cycle arrest probably acted as a key role in TCPP20+TCEP20-induced cytotoxicity and pyroptosis in HCECs. Our results suggested that TCPP20+TCEP20 co-exposure induced severer corneal damage, further illustrating its significance in estimating indoor health hazards to humans.

Indoor air pollution and human ocular diseases: Associated contaminants and underlying pathological mechanisms.

People spend a long time indoors, especially young children. The risk of indoor pollution on human health is one of the current hotspots in environmental and public health. The human ocular surface is highly susceptible to indoor environment quality. Epidemiological data have linked human ophthalmological disorders with exposure to indoor pollution. In this review, we summarized the adverse impacts of indoor pollution on the human ocular surface. Several studies demonstrated that indoor contaminants including particulate matter, volatile/semi-volatile organic compounds, heavy metals, and fuel combustion and cigarette smoke exposure were associated with the incidence of human dry eye, conjunctivitis, glaucoma, cataracts, age-related macular degeneration, and keratitis. In addition, toxicological investigations revealed that indoor pollution-induced induced chronic inflammation, oxidative damage, and disruption of tight junctions are the main underlying pathological mechanisms for ocular surface diseases. Taken together, this review may expand the understanding of pollution-induced eye disorder and highlight the importance of reducing associated contaminants to decrease their detrimental effects on human eyes.

Visual and optical performance of eyes with different corneal spherical aberration implanted with aspheric intraocular lens.

AIM: To compare the visual and optical performance of eyes with different corneal spherical aberration (SA) implanted with spherical aberration-free intraocular lens (IOLs). METHODS: Thirty-six patients with different corneal SA had phacoemulsification with implantation of spherical aberration-free IOLs. Patients were divided into 3 groups according to the value of preoperative corneal SA. Eyes with corneal SA <0.10µm were assigned to group A, those with 0.10 ≤corneal SA <0.20µm to Group B, and those with 0.20≤ corneal SA <0.35µm to Group C. Best-corrected visual acuity (BCVA), contrast sensitivity, corneal SA, total ocular aberrations, and depth of focus were recorded 3 months postoperatively. Distance-corrected near and intermediate visual acuity was studied to measure depth of focus. RESULTS: BCVA and contrast sensitivity were similar between groups. There were no significant differences in distance-corrected near or intermediate visual acuity. Corneal SA was similar before and 3 months after surgery in the 3 groups. With a 5.0mm pupil diameter, root mean square values for total ocular higher-order aberrations (HOAs) were lower in groups A and B than in group C. Total ocular SA was lower in group A than in groups B and C. SA was also lower in group B than in group C. Coma and trefoil were similar between the groups. CONCLUSION: Implantation of spherical aberration-free IOLs in eyes with different corneal SA results in similar visual performance at BCVA, contrast sensitivity and depth of focus.

[Current studies on induced pluripotent stem cells in retinal degenerative diseases].

Retinal degeneration diseases are a group of severe eye diseases that can lead to blindness. They are characterized by degeneration and apoptosis of photoreceptor cells and still lacking effective therapeutic procedures. Pluripotent stem cells (induced pluripotent stem cells, iPS cells) obtained from somatic cell reprogramming are similar to the embryonic stem cells (embryonic stem cells, ES cells), which have unlimited proliferation, differentiation and memory characteristics. Retinal cells from iPS cells have been used in cell transplantation for the treatment of retinal diseases, for the study of pathogenesis and drug toxicity evaluation in retinal degenerative diseases. This may provide new ideas and novel procedures for the treatment of retinal degenerative diseases in the future.

[Differential expression and significance of complement C4b and transthyretin in proliferative vitreoretinopathy].

OBJECTIVE: To investigate the differential expression of complement C4b and transthyretin in proliferative vitreoretinopathy (PVR). METHODS: It was a controlled experimental study. Human vitreous samples of 5 patients with PVR were analyzed by using two-dimensional gel electrophoresis and mass spectrometry, and the results were compared with those from normal control vitreous obtained from donor eyes. An in vivo model of PVR was created by intravitreous injection of cultured rabbit retinal pigment epithelial (RPE) cells. The vitreous of PVR models were analyzed by enzyme linked immunosorbent assay (ELISA) to confirm the proteomic results from the PVR patients. RESULTS: Seventy nine various proteins were expressed differently between PVR and normal vitreous, among which nine up-regulated proteins including complement C4b, transthyretin (TTR), and 7 albumins were identified by mass spectrometry. The up-regulation of complement C4b and TTR in PVR patients was also confirmed by ELISA. The concentration of complement C4b and TTR in normal vitreous were (20.18 ± 1.97) mg/L and (88.58 ± 8.84) mg/L respectively, in PVR patients were (38.1 ± 5.79) mg/L and (112.57 ± 6.89) mg/L respectively, difference significantly between these two groups (C4b: t = 11.54, TTR:t = 9.24; P < 0.05). CONCLUSIONS: Differences of complement C4b and TTR expression were observed between PVR and normal vitreous. These results have lead to the assumption that there is a connection between elevated concentrations of both complement C4b and TTR and the pathogenesis of PVR and further studies on the functions of these proteins are required.

[Progress in gene therapy study of Leber congenital amaurosis].

Leber congenital amaurosis (LCA) is an early onset retinal dystrophy that causes severe visual impairment. With the development of molecular genetics and the therapeutic gene replacement technology, the adeno-associated viral (AAV) vector-mediated gene therapy for LCA achieved encouraging progress in the past decade. The success of the Phase I clinical trials of human RPE65 gene therapy for LCA II patients makes it a pioneer in the field of retinal gene therapy and brings light to the cure of other hereditary retinopathy. This article briefly reviews the recent developments in the preclinical animal experiments and Phase I clinical trials for LCA.

[To carry out studies on treatment of hereditary retinal diseases with gene therapy in China].

Hereditary retinal diseases (HRD) are a group of both common and severe ocular hereditary diseases. HRD are a major cause of blindness. Human genetic resources in China are plentiful. Through the accomplishment of the human genome project and the widespread application of related genetic techniques, the methods for detecting the mutant genes of HRD has been established, and important findings in the treatment of HRD through gene therapy studies have been obtained. In the past ten years, HRD studies in China have gained significant progress in this field, including several pioneer results in the detection of autosomal dominant retinitis pigmentosa mutant gene. However, significant difference still exists in basic and clinical studies of HRD between the western countries and China. At present, HRD are transforming from "the incurable disease" to "the curable disease". Advancements in gene therapy studies are making the treatment of HRD possible, we should take advantage of these technological innovations to launch our own clinical trials using gene therapy in the treatment of HRD in Chinese patients as soon as possible.

[Progress in gene studies of hereditary retinal diseases].

Hereditary retinal diseases (HRDs), including retinitis pigmentosa, Leber's congenital amaurosis, congenital stationary night blindness, vitelliform macular dystrophy, Stargardt macular dystrophy, etc., are the most common and severe hereditary ocular diseases, which are closely associated with blindness. With the accomplishment of human genome project and the widespread application of genetic study techniques, the way leading to understanding of gene mutations of HRDs has been paved. Many encouraging breakthroughs of gene therapy studies have been made. Among them, the arrayed primer extension chip (Apex) technology greatly improved the efficiency of mutant gene screening of HRDs. Till now, 46 pathogenic genes and 2497 mutation loci have been identified to be related to HRDs. Gene therapy is one of the key treatments for HRDs. The disease causing mutant gene must be detected before the application of gene therapy. This paper reviews the latest progress in the study of gene mutations in HRDs.

Anterior segment complications after phacoemu-lsification combined vitrectomy and foldable intraocular lens implantation.

AIM: To evaluate the anterior segment complications of phacovitrectomy and foldable intraocular lens (IOL) implantation in eyes with significant cataract and co-existing vitreoretinal diseases. METHODS: This retrospective study was consisted of 285 eyes of 238 patients with various vitreoretinal abnormalities and visually significant cataracts. Vitreoretinal surgery was combined with phacoemulsification and foldable IOL implantation. Main outcome measures were visual acuity, the preoperative data, and the anterior segment complications at postoperative 6 to 72 months. RESULTS: The most common indications for surgery were non-diabetic vitreous hemorrhage, proliferative diabetic retinopathy. Preoperative vision ranged from 20/30 to light perception and postoperative vision ranged from 20/20 to no light perception. Postoperatively, in 245 eyes (85.9%), visual acuity improved by 3 lines or more on the Snellen chart. In 24 eyes (8.4%), vision remained within 3 lines of preoperative levels and in 16 eyes (5.6%), vision had decreased at the last follow-up. The most common anterior segment pathological change was PCO in 50 eyes (17.5%), the second was corneal edema in 32 eyes (11.2%) and the third was elevated IOP in 31 eyes (10.8%). CONCLUSION: The combined vitreoretinal surgery and phacoemulsification with foldable IOL implantation is safe and effective.