AMPK/MFF Activation: Role in Mitochondrial Fission and Mitophagy in Dry Eye.

Purpose: To assess the role of mitochondrial morphology and adenosine monophosphate-activated protein kinase (AMPK)/mitochondrial fission factor (MFF) in dry eye and the underlying mechanisms. Methods: Immortalized human corneal epithelial cells (HCECs) and primary HCECs were cultured under high osmotic pressure (HOP). C57BL/6 female mice were injected subcutaneously with scopolamine. Quantitative real-time PCR was used to measure mRNA expression. Protein expression was assessed by western blot and immunofluorescence staining. Mitochondrial morphology was observed by confocal microscopy and transmission electron microscopy. Results: First, HOP induced mitochondrial oxidative damage to HCECs, accompanied by mitochondrial fission and increased mitophagy. Then, AMPK/MFF pathway proteins were increased consequent to HOP-induced energy metabolism dysfunction. Interestingly, the AMPK pathway promoted mitochondrial fission and mitophagy by increasing the recruitment of dynamin-related protein 1 (DRP1) to the mitochondrial outer membrane in the HOP group. Moreover, AMPK knockdown attenuated mitochondrial fission and mitophagy due to HOP in HCECs. AMPK activation triggered mitochondrial fission and mitophagy. Mitochondrial fission of HCECs stressed by HOP was mediated via MFF phosphorylation. MFF knockdown reversed mitochondrial fragmentation and mitophagy in HCECs treated with HOP. Inhibition of MFF protected HCECs against oxidative damage, cell death, and inflammation in the presence of HOP. Finally, we detected mitochondrial fission and AMPK pathway activation in vivo. Conclusions: The AMPK/MFF pathway mediates the development of dry eye by positively regulating mitochondrial fission and mitophagy. Inhibition of mitochondrial fission can alleviate oxidative damage and inflammation in dry eye and may provide experimental evidence for treating dry eye.

Mussel-Inspired Microgel Encapsulated NLRP3 Inhibitor as a Synergistic Strategy Against Dry Eye.

The inflammatory response mediated by oxidative stress is the main pathogenesis of dry eye, but clinical observations have shown that scavenging oxygen-free radicals alone has limited therapeutic effect. Moreover, the unique anatomy and physiology of the ocular surface result in low bioavailability of drugs, and higher concentration is required to achieve the desired efficacy, which, however, may bring systemic side effects. These problems pose a challenge, but the revelation of the ROS-NLRP3-IL-1ß signaling axis opens up new possibilities. In this investigation, an NLRP3 inhibitor was successfully encapsulated in polydopamine-based microgels and used for dry eye treatment. It was demonstrated that the well-designed microgels exhibited good biocompatibility, prolonged drug retention time on the ocular surface, and effective inhibition of corneal epithelial damage and cell apoptosis. In addition, due to the synergistic effect, the NLRP3 inhibitor-loaded microgels could exert enhanced oxygen radical scavenging and inflammation-inhibiting effects at a lower dose than monotherapy. These findings suggest that polydopamine-based microgels have advantages as ocular surface drug delivery platforms and have promising applications in oxidative damage-related inflammatory diseases in synergy with anti-inflammatory drugs.

Topography-Guided Versus Wavefront-Optimized LASIK for Myopia With and Without Astigmatism: A Meta-analysis.

PURPOSE: To evaluate the differences in efficacy, predictability, safety, and visual quality between topography-guided customized ablation treatment (TCAT) and wavefront-optimized (WFO) laser in situ keratomileusis (LASIK) for the treatment of myopia with and without astigmatism. METHODS: A comprehensive literature search of PubMed, Embase, the Cochrane library, Web of Science, and ClinicalTrials was used to identify randomized controlled trials (RCTs) comparing TCAT-LASIK with WFO-LASIK for myopia with and without astigmatism up to September 2020. The references of all searched literature were checked as supplements. Literature was screened according to the inclusion and exclusion criteria and relative data were extracted. RevMan software version 5.3.0 (Cochrane Collaboration) was used for meta-analysis. RESULTS: A total of seven RCTs (1,168 eyes) were included. There were no statistically significant differences in the ratio of uncorrected distance visual acuity of 20/20 or better (relative risk [RR] = 1.01, 95% CI [0.97 to 1.06], P = .64) and 20/16 or better (RR = 0.96, 95% CI [0.80 to 1.16], P = .69). Compared with WFO-LASIK, TCAT-LASIK achieved a higher proportion of postoperative manifest refractive spherical equivalent within ±0.50 diopters of the target (RR = 1.06, 95% CI [1.02 to 1.11], P = .003) and less surgically induced higher order aberrations (weighted mean difference [WMD] = -0.11, 95% CI [-0.15 to -0.0], P < .00001), spherical aberrations (WMD = -0.04, 95% CI [-0.05 to -0.03], P < .00001), and coma (WMD = -0.15, 95% CI [-0.28 to -0.01], P = .03). No patient lost two or more lines of distance-corrected visual acuity postoperatively in the two groups. CONCLUSIONS: This meta-analysis suggests that both TCATLASIK and WFO-LASIK show excellent efficacy, predictability, and safety for myopia. TCAT-LASIK exhibited more accurate postoperative refraction predictability and less surgically induced higher order aberrations, spherical aberrations, and coma. More randomized, prospective, and large sample-sized studies are needed to confirm these conclusions in the long term. [J Refract Surg. 2021;37(10):707-714.].