Novel mutation in EFEMP1 identified from two Chinese POAG families differentially activated endoplasmic reticulum stress markers and induced glaucoma in mouse.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma. Using whole-exome sequencing, we identified two independent families diagnosed as POAG from the China with a novel EFEMP1 variant (Exon3, c.175A>C p.Met59Leu); Three previously reported variants c.1160G>A p.R387Q, c.1189T>C p.Y397H, and c.1429C>T p.R477C in EFEPM1 from 55 sporadic POAG individuals were also identified. The variant c.175A>C p.Met59Leu co-segregated with the disease phenotype within the families. Immunoprecipitation and western blot assays showed that all three EFEMP1 mutants (p.Met59Leu, pArg140Trp, pArg345Trp) increased intracellular protein aggregations, and pMet59Leu and pArg140Arg also enhanced their extracellular proteins secretion, compared to WT in HEK293T. The differential regulations to endoplasmic reticulum (ER) stress markers ATF4, GPR78/94, and CHOP, and differential phosphorylation activations to CREB at Ser133, AKT at Ser473, p44/42 at Thr202/Tyr204, and STAT3 at Tyr705, were also detected among the mutants and WT. Finally, we revealed a significant increment of intraocular pressure and obvious reduction of RGC cells at the sixth week following intravitreal injection of adenovirus 5 (Ad5) expressing in pMet59Leu compared to WT and GFP controls. Together, variant c.175A>C p.Met59Leu in EFEMP1 is pathogenic and different mutants in EFEMP1 triggered distinct signaling pathways, explaining the reason of mutation-dependent disease phenotypes of EFEMP1.

Detection of mutations in MYOC, OPTN, NTF4, WDR36 and CYP1B1 in Chinese juvenile onset open-angle glaucoma using exome sequencing.

Juvenile onset open-angle glaucoma (JOAG) affects patients before 40 years of age, causing high intraocular pressure and severe optic nerve damage. To expand the mutation spectrum of the causative genes in JOAG, with a view to identify novel disease-causing mutations, we investigated MYOC, OPTN, NTF4, WDR36 and CYP1B1 in a cohort of 67 unrelated Chinese JOAG patients. Whole exome sequencing was used to identify possible pathogenic mutations, which were further excluded in normal controls. After sequencing and the use of a database pipeline, as well as predictive assessment filtering, we identified a total of six mutations in three genes, MYOC, OPTN and CYP1B1. Among them, 2 heterozygous mutations in MYOC (c. 1109C > T, p. (P370L); c. 1150G > C, p. (D384H)), 2 heterozygous mutations in OPTN (c. 985A > G, p.(R329G); c. 1481T > G, p. (L494W)) and 2 homozygous mutations in CYP1B1 (c. 1412T > G, p.(I471S); c. 1169G > A, p.(R390H)) were identified as potentially causative mutations. No mutation was detected in NTF4 or WDR36. Our results enrich the mutation spectra and frequencies of MYOC, OPTN and CYP1B1 in JOAG among the Chinese population. Further studies are needed to address the pathogenicity of each of the mutations detected in this study.

Soft Bandage Contact Lenses in Management of Early Bleb Leak Following Trabeculectomy.

PURPOSE: To investigate the efficacy of a soft bandage contact lens in the management of early bleb leak following trabeculectomy. METHODS: Between October 2011 and April 2013, 11 patients with early bleb leak following fornix-based trabeculectomy were instructed to wear a soft bandage contact lens 14 mm in diameter continuously for 1-2 weeks. The daily visual acuity, intraocular pressure (IOP), anterior chamber situation, and healing condition were measured at 1, 3, and 7 d, after con tact lens removal, and 3 months after trabeculectomy. The conditions of blebs, sensation of wearing contact lens, and adverse events were recorded. RESULTS: Bleb leaks were observed at 2-8 d after surgery, (4.09 ± 1.10 d on average). The daily LogMAR visual acuity did not significantly differ before and after contact lens wear (P > 0.05). The IOP was significantly raised after at 1, 3, and 7 d after lens wear (all P < 0.05).The IOP at 3 months after lens wear did not significantly differ from that measured at lens removal (t = 1.191, P = 0.089). At 1 d after lens wear, 6 cases had deeper anterior chambers. All patients presented with a significantly deepened anterior chamber at 3 d after lens wear, and were restored to the preoperative conditions. The bleb leakage was successfully treated at 7 d after lens removal in 10 patients, while 1 patient had to wear the contact lens for another 7 d for full healing of the bleb leak. No ocular infection was noted throughout the management. CONCLUSION: A soft bandage contact lens of 14 mm diameter is a safe and efficacious therapy for an early bleb leak following fornix-based trabeculectomy.

The safety and efficacy of modified minimally invasive trabeculectomy for the treatment of primary chronic angle-closure glaucoma.

BACKGROUND: Primary chronic angle-closure glaucoma (PCACG) is one of the main types of glaucoma in China. Trabeculectomy is the most commonly used glaucoma filtration surgery for glaucoma in the world. Conventional trabeculectomy is prone to anesthesia-related complications intraoperative and operation-related complications postoperative in PCACG treatment. Modified minimally invasive trabeculectomy maybe can reduce the incidence of complications. METHODS: We conducted a prospective case series study and performed modified fornix-based trabeculectomy in 27 patients (30 eyes) under topical anesthesia; we then observed intraoperative anesthesia and cooperation effect, intraoperative and postoperative complications, preoperative and postoperative visual acuity, intraocular pressure (IOP), visual field, and the use of ocular hypotensive drugs. The patients were followed up for at least 12 months. RESULTS: All operations were completed successfully with no intraoperative complications. All 27 patients (30 eyes) were followed up for at least 12 months. No significant decrease in visual acuity was observed at days 1 or 7 and at months 1, 3, 6, and 12 after operation; however, a significant decrease in IOP was observed at days 1 and 7 and at months 1, 3, 6, and 12 after operation. Moreover, no significant progression in visual field mean defect was observed at month 12 after operation, and the number of ocular hypotensive drugs required was significantly reduced at months 6 and 12 after operation. By month 12 after operation, the overall success rate was 93.33% (28/30). CONCLUSIONS: Modified minimally invasive trabeculectomy is safe and effective for the treatment of PCACG.