The role of corneal endothelium in macular corneal dystrophy development and recurrence.

Macular corneal dystrophy (MCD) is a progressive, bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6 (CHST6). Corneal transplantation is the ultimate therapeutic solution for MCD patients. Unfortunately, postoperative recurrence remains a significant challenge. We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK). Our results revealed that the recurrence rate was nearly three times higher in the DALK group (39.13%, 9/23 eyes) compared with the PKP group (10.89%, 11/101 eyes), suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence. Our experimental data confirmed the robust mRNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium. Selective knockdown of wild-type Chst5 in mouse corneal endothelium (ACsiChst5), but not in the corneal stroma, induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients. Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD, along with corneal endothelial abnormalities. Intracameral injection of wild-type Chst5 rescued the corneal impairments in ACsiChst5 mice and retarded the disease progression in Chst5 mutant mice. Overall, our study provides new mechanistic insights and therapeutic approaches for MCD treatment by high-lighting the role of corneal endothelium in MCD development.

Genomic instability and eye diseases.

Background: Genetic information is stored in the bases of double-stranded DNA. However, the integrity of DNA molecules is constantly threatened by various mutagenic agents, including pollutants, ultraviolet light (UV), and medications. To counteract these environmental damages, cells have established multiple mechanisms, such as producing molecules to identify and eliminate damaged DNA, as well as reconstruct the original DNA structures. Failure or insufficiency of these mechanisms can cause genetic instability. However, the role of genome stability in eye diseases is still under-researched, despite extensive study in cancer biology. Main text: As the eye is directly exposed to the external environment, the genetic materials of ocular cells are constantly under threat. Some of the proteins essential for DNA damage repair, such as pRb, p53, and RAD21, are also key during the ocular disease development. In this review, we discuss five ocular diseases that are associated with genomic instability. Retinoblastoma and pterygium are linked to abnormal cell cycles. Fuchs' corneal endothelial dystrophy and age-related macular degeneration are related to the accumulation of DNA damage caused by oxidative damage and UV. The mutation of the subunit of the cohesin complex during eye development is linked to sclerocornea. Conclusions: Failure of DNA damage detection or repair leads to increased genomic instability. Deciphering the role of genomic instability in ocular diseases can lead to the development of new treatments and strategies, such as protecting vulnerable cells from risk factors or intensifying damage to unwanted cells.

Overactivation of Norepinephrine-ß2-Adrenergic Receptor Axis Promotes Corneal Neovascularization.

Purpose: To investigate the role of the sympathetic nervous system in corneal neovascularization (CNV) and to identify the downstream pathway involved in this regulation. Methods: Three types of CNV models were constructed with C57BL/6J mice, including the alkali burn model, suture model, and basic fibroblast growth factor (bFGF) corneal micropocket model. Subconjunctival injection of the sympathetic neurotransmitter norepinephrine (NE) was administered in these three models. Control mice received injections of water of the same volume. The corneal CNV was detected using slit-lamp microscopy and immunostaining with CD31, and the results were quantified by ImageJ. The expression of ß2-adrenergic receptor (ß2-AR) was stained with mouse corneas and human umbilical vein endothelial cells (HUVECs). Furthermore, the anti-CNV effects of ß2-AR antagonist ICI-118,551 (ICI) were examined with HUVEC tube formation assay and with a bFGF micropocket model. Additionally, partial ß2-AR knockdown mice (Adrb2+/-) were used to establish the bFGF micropocket model, and the corneal CNV size was quantified based on the slit-lamp images and vessel staining. Results: Sympathetic nerves invaded the cornea in the suture CNV model. The NE receptor ß2-AR was highly expressed in corneal epithelium and blood vessels. The addition of NE significantly promoted corneal angiogenesis, whereas ICI effectively inhibited CNV invasion and HUVEC tube formation. Adrb2 knockdown significantly reduced the cornea area occupied by CNV. Conclusions: Our study found that sympathetic nerves grow into the cornea in conjunction with newly formed vessels. The addition of the sympathetic neurotransmitter NE and activation of its downstream receptor ß2-AR promoted CNV. Targeting ß2-AR could potentially be used as an anti-CNV strategy.

Questionnaire Analysis on Incidence and Risk Factors of Dry Eye in Children From a Myopia Outpatient Clinic.

OBJECTIVE: To analyze the incidence and risk factors of dry eye in children from a myopia outpatient clinic via a questionnaire and Keratograph 5M. METHODS: A cross-sectional study was performed. sThere were 214 children (428 eyes) selected from the myopia outpatient clinic of the affiliated Eye Hospital of Shandong First Medical University from July 2021 to September 2021, including 105 boys (210 eyes) and 109 girls (218 eyes), with an average age of 10.1 ± 2.5 years. The incidence rate and influence factors for dry eye were calculated. RESULTS: Thirty-four of 214 children were diagnosed with dry eye, accounting for 15.9% of the patients. The correlation between fussy eating and the tear meniscus height was statistically significant (Z = -2.158, p = 0.039), along with the correlation between short-distance use of eyes and the tear meniscus height (Z = -2.135, p = 0.033). The degree of meibomian gland deficiency was graded. The meibomian gland was graded as grade 1 in 242 eyes (68.9%), grade 2 in 104 eyes (29.6%), and grade 3 in 5 eyes (1.4%). There was a significant difference in the correlation between eye rubbing and the incidence of dry eye in children (Z = -2.747, p = 0.008). There was also a significant difference in the correlation between picky eating and the incidence of dry eye in children (Z = -2.347; p = 0.024). There was a statistically significant correlation between the time of looking at electronic products and the morphology of the meibomian gland (Z = -2.201, p = 0.028). The results showed that the effect of mild and moderate ametropia on the non-invasive tear breakup time in children was statistically significant (Z = -2.027; p = 0.043). CONCLUSION: There is a high incidence of dry eye in children in the myopia outpatient clinic. There is a significant correlation between picky eating, eye rubbing, and the incidence of dry eye. Looking at electronic products for a long time will also affect the morphology of the meibomian gland in children.