Comprehensive management of post-LASIK ectasia: From prevention to treatment.

Post-laser in situ keratomileusis (post-LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high-fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross-linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long-term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide.

Changes of the effective optical zone after small-incision lenticule extraction and a correlation analysis.

The objective of the study is to observe the changes in the effective optical zone (EOZ) after small incision lenticule extraction (SMILE) and explore possible correlations with some influencing factors. In total, 133 eyes after SMILE were divided into the mild to moderate myopia group (- 1.75 D to - 5.75 D, 70 eyes) and the high myopia group (- 6.00 D to - 9.50 D, 63 eyes). The postoperative EOZ was calculated by utilizing the corneal tangential curvature map. Changes in EOZ (△-OZ) were monitored and compared between the two groups. Pearson correlation analysis was conducted to determine the correlation between △-OZ and corneal high-order wavefront aberrations. Multicollinearity analysis and ridge regression analysis were performed to assess the correlation between △-OZ and some corneal parameters. After SMILE, the horizontal EOZ (H-EOZ), vertical EOZ (V-EOZ), and average EOZ (A-EOZ) were significantly smaller than the programmed optical zone (POZ) in both groups (p < 0.05). The difference between V-EOZ and POZ (△V-OZ) and the difference between A-EOZ and POZ (△A-OZ) showed more significant changes in the high myopia group than in the mild to moderate myopia group, and △V-OZ was significantly larger than the difference between H-EOZ and POZ (△H-OZ) in the high myopia group. In both groups, the total high-order aberration (T-HOA) and spherical aberration (SA) both increased after SMILE, and they had a similar significant negative correlation with A-EOZ. Moreover, there was a significant negative correlation between △-OZ and Km (X1), Q-value (X2), spherical equivalent (SE, X3), ablating depth (AD, X4) and △e (X6), and a significant positive correlation between △-OZ and △Q (X5). △H-OZ was expressed as Y1, △V-OZ as Y2, and △A-OZ as Y3. The multiple linear regression equations were as follows: Y1 = 3.683 - 0.065X1, Y2 = 1.549 - 0.469X2 - 0.059X3, Y3 = 4.015 - 0.07X1 - 0.03X3, Y1 = 1.337 - 0.005X4 + 0.413X5, Y2 = 1.265 + 0.469X5, and Y3 = 0.852 - 0.002X4 - 0.398X6. The correlation degree with △A-OZ was ranked as Km > △Q > Q-value > AD > e-value > △e > SE > △Km, as represented by the ridge regression analysis. The EOZ was irregularly reduced after SMILE, which should be taken into consideration in the design of POZ, especially for high myopia. Consideration of the refractive diopter and corneal topography is advised for the design of POZ, the latter of which has greater reference significance.

Mechanisms of NO-Mediated Protein S-Nitrosylation in the Lens-Induced Myopia.

Background: Myopia is a chronic ocular disease, emerging as the most common type of refractive error. This study intends to preliminarily explore the roles of protein S-nitrosylation of nitric oxide (NO) in the regulation of myopia by detecting the expression of neuronal nitric oxide synthase (nNOS) and downstream S-nitrosylation, using the animal model of lens-induced myopia (LIM) in mice. Methods: The 3-week-old C57BL/6 J mice were divided into three groups: group I, lens-induced 0-week group (take eyeballs at the age of 3 weeks); group II, self-control eyes of experimental group (take eyeballs at the age of 7 weeks); and group III, lens-induced 4-week group (take eyeballs at the age of 7 weeks). The diopter and axial length of each group were measured by streak retinoscopes and optical coherence tomography (OCT) before and after model establishment. The protein expressions and locations of nNOS and S-nitrosylated proteins (PSNOs) were measured by western blot and immunofluorescence staining. Site-specific proteomic for protein S-nitrolysation was used to detect the existence and location of S-nitrosylation proteins in the retina of myopic and nonmyopic mice. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and motif enrichment analyses were performed. The differential sites were analyzed by GO, KEGG, and motif. Irreversible biotinylation procedure combined with protein purification and western blot was used to detect the protein expression of α-enolase (ENO1), a key player in the hypoxia-related signal pathway. Results: The expressions of nNOS and PSNOs were significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. A total of 595 S-nitrosylated proteins, 709 S-nitrosylated peptides, and 708 S-nitrosylated sites were identified by site-specific S-nitrolysation proteomics in the retina of myopic and control eyes. A total of 19 differentiation loci were screened, of which 13 sites were downregulated and 6 sites were upregulated in experimental eyes compared with the self-control group. Specifically, the expression of SNO-ENO1 was significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. Conclusion: LIM induces the decrease of nNOS and PSNO protein levels in the retina of myopic mice. NO-mediated nonclassical protein S-nitrosylation modification may play an important role in the regulation of lens-induced myopia. ENO1 may be a key factor in the regulation of S-nitrosylation modification of myopia.

Correction of presbyopia. / 老视的矫治方法.

Presbyopia, a progressive visual difficulty caused by weakened physiological regulation, is one of the main causes of visual impairment in people over 40 years old. Currently, the main methods of correction of presbyopia include optical correction, surgical correction, and drug treatment, which can improve the visual nearness disorder to some extent. Optical correction is the most common way with advantages of safety, which can adjust the lens parameters at any time, while cause kinds of inconvenience in life by wearing and taking off glasses frequently. Surgical intervention, including corneal surgery, lens surgery and scleral surgery, with certain advantages and disadvantages in each operation style. New pharmaceutical agents are expected to be a new and effective method for the treatment of presbyopia, but it lacks multicenter randomized controlled trials and evidence-based medicine evidence to evaluate the safety and effectiveness.

RNA-sequencing analysis reveals the long noncoding RNA profile in the mouse myopic retina.

Aim: Myopia is a prevalent public health problem. The long noncoding RNA (lncRNA) mechanisms for dysregulated retinal signaling in the myopic eye have remained elusive. The aim of this study was to analyze the expression profiles and possible pathogenic roles of lncRNAs in mouse form-deprived myopia (FDM) retinas. Methods: A mouse FDM model was induced and retinas from the FDM right eyes and the contralateral eyes were collected for RNA sequencing. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and lncRNA-mRNA coexpression network analyses were conducted to explore the biological functions of the differentially expressed lncRNAs. In addition, the levels of differentially expressed lncRNAs in the myopic retinas were validated by quantitative real-time PCR (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to detect the localization of lncRNAs in mouse retinas. Results: FDM eyes exhibited reduced refraction and increased ocular axial length compared to control fellow eyes. RNA sequencing revealed that there were 655 differentially expressed lncRNAs between the FDM and control retinas. Functional enrichment analysis indicated that the differentially expressed RNAs were mostly enriched in cellular processes, cytokine-cytokine receptor interactions, retinol metabolism, and rhythmic processes. Differentially expressed lncRNAs were validated by qRT-PCR. Additionally, RNA FISH showed that XR_384718.4 (Gm35369) localized in the ganglion cell (GCL) and inner nuclear layers (INL). Conclusion: This study identified the differential expression profiles of lncRNAs in myopic mouse retinas. Our results provide scientific evidence for investigations of myopia and the development of putative interventions in the future.

Comparison of Efficacy and Safety Between Standard, Accelerated Epithelium-Off and Transepithelial Corneal Collagen Crosslinking in Pediatric Keratoconus: A Meta-Analysis.

Purpose: The purpose of the study is to compare the efficacy of standard epithelium-off CXL (SCXL), accelerated epithelium-off CXL (ACXL), and transepithelial crosslinking CXL (TECXL) for pediatric keratoconus. Methods: A literature search on the efficacy of SCXL, ACXL, and TECXL [including accelerated TECXL (A-TECXL)] for keratoconus patients younger than 18 years was conducted using PubMed, Cochrane Library, ClinicalTrials.gov, and EMBASE up to 2021. Primary outcomes were changes in uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) after CXL. Secondary outcomes were changes in best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), and central corneal thickness (CCT). Estimations were analyzed by weighted mean difference (WMD) and 95% confidence interval (CI). Results: A number of eleven identified studies enrolled 888 eyes (SCXL: 407 eyes; ACXL: 297 eyes; TECXL: 28 eyes; A-TECXL: 156 eyes). For pediatric keratoconus, except for a significant greater improvement in BCVA at 24-month follow-up in SCXL (WMD = -0.08, 95%CI: -0.14 to -0.01, p = 0.03, I2 = 71%), no significant difference was observed in other outcomes between the SCXL and ACXL groups. SCXL seems to provide greater changes in UCVA (WMD = -0.24, 95% CI: -0.34 to -0.13, p < 0.00001, I2 = 89%), BCVA (WMD = -0.09, 95% CI: -0.15 to -0.04, p = 0.0008, I2 = 94%), and Kmax (WMD = -1.93, 95% CI: -3.02 to -0.85, p = 0.0005, I2 = 0%) than A-TECXL, with higher incidence of adverse events. Conclusion: For pediatric keratoconus, both SCXL and ACXL appear to be comparable in the efficacy of visual effects and keratometric outcomes; SCXL seems to provide greater changes in visual and pachymetric outcomes than A-TECXL.

Polymicrobial keratitis after accelerated corneal collagen cross-linking in keratoconus: Case reports and literature review.

PURPOSE: To report two cases of polymicrobial keratitis following corneal collagen cross-linking for keratoconus and to review the literature. METHODS: Retrospective case note and literature review. RESULTS: The first case involved a 27-year-old male who presented with amebic corneal ulcers 3 days after the collagen cross-linking procedure. Some gram-negative (gram-ve) cocci were found upon staining, and cysts were observed by confocal microscopy at 7 days after surgery. Acanthamoeba infection mixed with gram-ve organisms was diagnosed. In the second case, a 14-year male developed Staphylococcus aureus corneal infection with anterior chamber empyema 3 days after the collagen cross-linking procedure for keratoconus. Occasional gram-positive (gram + ve) cocci and gram-ve bacilli were observed under a microscope. The mixed keratitis in the two patients resolved after systemic and topical antibiotic therapy, but the infection ultimately resulted in corneal scarring. Follow-up keratoplasty was needed to improve vision acuity in both patients. CONCLUSION: Although ultraviolet irradiation and the reactive oxygen released by riboflavin during collagen cross-linking have bactericidal effects, a lack of a corneal epithelial barrier, bandage contact lens usage, perioperative hygiene, and an abnormal immune state are risk factors for infectious keratitis after collagen cross-linking. Perioperative management of collagen cross-linking is important to prevent infection.

Transneuronal Degeneration in the Visual Pathway of Rats following Acute Retinal Ischemia/Reperfusion.

The maintenance of visual function not only requires the normal structure and function of neurons but also depends on the effective signal propagation of synapses in visual pathways. Synapses emerge alterations of plasticity in the early stages of neuronal damage and affect signal transmission, which leads to transneuronal degeneration. In the present study, rat model of acute retinal ischemia/reperfusion (RI/R) was established to observe the morphological changes of neuronal soma and synapses in the inner plexiform layer (IPL), outer plexiform layer (OPL), and dorsal lateral geniculate nucleus (dLGN) after retinal injury. We found transneuronal degeneration in the visual pathways following RI/R concretely presented as edema and mitochondrial hyperplasia of neuronal soma in retina, demyelination, and heterotypic protein clusters of axons in LGN. Meanwhile, small immature synapses formed, and there are asynchronous changes between pre- and postsynaptic components in synapses. This evidence demonstrated that transneuronal degeneration exists in RI/R injury, which may be one of the key reasons for the progressive deterioration of visual function after the injury is removed.

Comparison of the optical quality after SMILE and FS-LASIK for high myopia by OQAS and iTrace analyzer: a one-year retrospective study.

BACKGROUND: To compare the correction effect and optical quality after small-incision lenticule extraction (SMILE) and femtosecond laser assisted laser in situ keratomileusis (FS-LASIK) for high myopia. METHODS: 51 high myopia eyes after SMILE and 49 high myopia eyes after FS-LASIK were enrolled and divided into two groups retrospectively. The OQAS and iTrace analyzer were used for optical quality inspection. Between the two groups the spherical equivalent (SE), astigmatism, uncorrected distant visual acuity (UDVA), strehl ratio (SR), modulation transfer function cutoff frequency (MTF cutoff), objective scatter index (OSI) and wavefront aberrations were analyzed and compared before surgery and at 1, 6 and 12 months after surgery. RESULTS: After the operation: (1) SE and astigmatism declined and UDVA increased significantly in both groups, and UDVA was better after SMILE than FS-LASIK. (2) SR and MTF cutoff reduced and OSI increased significantly after SMILE and FS-LASIK. SR and MTF cutoff were significantly higher after SMILE than FS-LASIK. OSI was significantly lower after SMILE than FS-LASIK. (3) The total wavefront aberration, total low-order wavefront aberration, defocus and astigmatism aberration as well as trefoil aberration reduced significantly in both groups. The total high-order wavefront aberration increased significantly after FS-LASIK. The spherical and coma aberration increased significantly in both groups. The total high-order wavefront aberration and coma aberration at 1 month were higher after FS-LASIK than SMILE. CONCLUSION: The optical quality descended after SMILE and FS-LASIK. SMILE was superior to FS-LASIK at the correction effect and optical quality for high myopia. The combination of OQAS and iTrace analyzer is a valuable complementary measurement in evaluating the optical quality after the refractive surgery. TRIAL REGISTRATION: This is a retrospective study. This research was approved by the ethics committee of Xiangya Hospital and the IRB approval number is 201612074.

Detection of Static and Dynamic Stereopsis after Femtosecond Laser Small Incision Lenticule Extraction for High Myopia.

PURPOSE: The purpose of this study is to test binocular visual function after femtosecond laser small incision lenticule extraction (SMILE) for high myopia. The traditional Titmus stereotest and dynamic stereotest based on the visual perception biological model were used for comparative analysis. METHODS: A total of 43 patients were enrolled in this prospective study. At Week 1, Month 1, and Month 3 after surgery, the Titmus stereotest and dynamic stereotest generated by MATLAB were conducted. Dynamic stereopsis consists of randomly flickering Gabor spots and is divided into two models of high energy and low energy according to flicker frequency. RESULTS: The preoperative manifest refraction spherical equivalent was -7.21 ± 0.70 D. The preoperative anisometropia was 0.52 ± 0.54D. The quartiles of static stereoacuity in preoperation and 3 follow-ups were as follows: 50.00 (25.00, 100.00) in preoperation, 63.00 (40.00, 63.00) at Week 1, 40.00 (32.00, 63.00) at Month 1, and 40.00 (25.00, 50.00) at Month 3. Static stereopsis improved at Month 1 and Month 3 compared with preoperation and Week 1 (P < 0.05). There were statistically significant differences in high energy dynamic stereopsis at Week 1 and Month 1 compared to preoperation (P < 0.05). In addition, significant differences in low energy dynamic stereopsis were detected between Month 1 and preoperation and also at Month 3 compared to Month 1 (P < 0.05). CONCLUSION: Most high myopia patients have a dynamic stereopsis deficiency before refractive correction. SMILE surgery can improve both static and dynamic stereopsis early in the postoperation period. However, in the long term, there is no significant difference or even a decrease in dynamic stereopsis.

A microscopic study of the corneal stromal lenticules extracted during femtosecond laser-assisted small incision lenticule extraction.

The aim of the present study was to investigate the histological and morphological characteristics of corneal stromal lenticules extracted during femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery by light and electron microscopy. A total of 20 human corneal stromal lenticules extracted during SMILE surgery were sent for microscopic examination immediately after surgery. Of these, six were observed under a light microscope and 14 were observed under an electron microscope. The smoothness of the front and rear surface of the lenticules observed under an electron microscope was rated on a scale of 0 to 4 according to unified evaluation criteria and the scores were statistically compared. Under the light microscope, the edge of the cross section of the corneal stromal lenticules was deeply stained and certain burrs and broken collagen fibers were observed. The swollen corneal stromal fibers were distributed irregularly, with a few bubbles of different sizes. Under the electron microscope, the surface of the lenticules ablated using a femtosecond laser was not perfectly smooth and the front surface was smoother than the rear surface. The side edge of the lenticules ablated using a femtosecond laser was not as regular as the edge cut using microscissors. Necrosis and dissolution of collagen fibers were observed near the surface of the lenticules. In conclusion, the surface quality of corneal stromal lenticules ablated using a femtosecond laser was not optimal when observed under a microscope. Increased attention should be paid to the histology and morphology of the corneal surface following laser ablation.

Clinical outcomes after small-incision lenticule extraction versus femtosecond laser-assisted LASIK for high myopia: A meta-analysis.

AIM: To compare postoperative clinical outcomes of high myopia after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). METHODS: From March 2018 to July 2020, PubMed, MEDLINE, Embase, the Cochrane Library, and several Chinese databases were comprehensively searched. The studies meeting the criteria were selected and included; the data were extracted by 2 independent authors. The clinical outcome parameters were analyzed with RevMan 5.3. RESULTS: This meta-analysis included twelve studies involving 766 patients (1400 eyes: 748 receiving SMILE and 652 receiving FS-LASIK). Pooled results revealed no significant differences in the following outcomes: the logarithm of the mean angle of resolution (logMAR) of postoperative uncorrected distance visual acuity (weighted mean difference (WMD) = -0.01, 95% confidence interval (CI): -0.02 to 0.00, I2 = 0%, P = 0.07 at 1 mo; WMD = -0.00, 95% CI: -0.01 to 0.01, I2 = 0%, P = 0.83 at 3 mo; WMD = -0.00, 95% CI: -0.01 to 0.00, I2 = 32%, P = 0.33 in the long term), and the postoperative mean refractive spherical equivalent (WMD = -0.03, 95% CI: -0.09 to 0.03, I2 = 13%, P = 0.30). However, the SMILE group had significantly better postoperative corrected distance visual acuity (CDVA) than the FS-LASIK group (WMD = -0.04, 95% CI, -0.05 to -0.02, I2 = 0%, P<0.00001). In the long term, postoperative total higher-order aberration (WMD = -0.09, 95% CI: -0.10 to -0.07, I2 = 7%, P<0.00001) and postoperative spherical aberration (WMD = -0.15, 95% CI: -0.19 to -0.11, I2 = 29%, P<0.00001) were lower in the SMILE group than in the FS-LASIK group; a significant difference was also found in postoperative coma (WMD = -0.05, 95% CI: -0.06 to -0.03, I2 = 30%, P<0.00001). CONCLUSION: For patients with high myopia, both SMILE and FS-LASIK are safe, efficacious and predictable. However, the SMILE group demonstrated advantages over the FS-LASIK group in terms of postoperative CDVA, while SMILE induced less aberration than FS-LASIK. It remains to be seen whether SMILE can provide better visual quality than FS-LASIK; further comparative studies focused on high myopia are necessary.

Clinical results of orthokeratology therapy in adolescents with low to moderate myopia. / é’å°‘å¹´ä½Žä¸­åº¦è¿‘è§†æ‚£è€ å¤œæˆ´è§’è†œå¡‘å½¢é•œçš„ä¸´åºŠæ•ˆæžœ.

OBJECTIVES: To observe the clinical results of orthokeratology therapy in adolescents with low to moderate myopia after wearing the lens for 6 months. METHODS: The data of 69 adolescents with low to moderate myopia were retrospectively analyzed. According to the degree of spherical power before treatment, the adolescents were divided into a low myopia group (34 cases, with spherical diopter from -3.00 to -0.75 D) and a moderate myopia group (35 cases, with spherical diopter from -5.75 to -3.25 D). The changes of the uncorrected distance visual acuity (UDVA), intraocular pressure, count of endothelial cell, eye axis length, Strehl ratio (SR), modulation transfer function (MTF), Q value, and wavefront aberrations before the treatment and 6 months after the treatment were compared and analyzed between the 2 groups. RESULTS: Compared with before the treatment, the UDVA improved significantly in the 2 groups (both P<0.05); the intraocular pressure and the count of endothelial cell did not change obviously in the 2 groups (all P>0.05), the eye axial length in the 2 groups was increased significantly (both P<0.05), but there was no significant difference between the 2 groups (all P>0.05); the Q value in the 2 groups was increased significantly, and the change was more obvious for the moderate myopia group (all P<0.05); the SR and MTF were increased remarkably in the 2 groups (all P<0.05), and there were no significant difference in the changes of SR and MTF between the 2 groups (both P>0.05); a considerable decrement was found for the total aberration, the total low-order aberration, and defocus (all P<0.05), and the changes were more significant in the moderate myopia group (all P<0.05); the total high-order aberrations were increased in the low myopia group (P<0.05); the increment of the vertical astigmatism, spherical aberration, horizontal coma, vertical coma, and horizontal trefoil were noticeable (all P<0.05), and the changes of the spherical aberration, vertical coma, and horizontal trefoil were more obvious in the moderate myopia group (all P<0.05). CONCLUSIONS: Orthokeratology can effectively improve the visual results of the adolescents with low to moderate myopia, and the corrective effect is more obvious for the adolescents with moderate myopia than those with low myopia.

One-year effect of wearing orthokeratology lenses on the visual quality of juvenile myopia: a retrospective study.

OBJECTIVE: To study the one-year effect of wearing orthokeratology (OK) lenses on the visual quality of juvenile myopia. METHODS: The right eyes of 36 juvenile myopias were retrospectively studied in this work. Q-value, e-value, corneal curvature, strehl ratio (SR), modulation transfer function (MTF) and wavefront aberration (WA) were compared before and at 1, 3 and 12 months after wearing OK lenses. The SR, MTF and WA of cornea, internal optic and ocular were analyzed separately. The spherical and cylinder diopter, vision acuity, compensating factor (CF) and compensative rate (CF%) were compared before and at 12 months after wearing OK lenses. RESULTS: (1) The vision of LogMAR increased and the corneal curvature decreased significantly after wearing OK lenses. There was no significant difference for the e-value before and after wearing OK lenses. The Q-value increased at 1 month but decreased at 3 and 12 months remarkably. (2) The ocular and internal optic SR and MTF increased significantly at 1 month and then remained stable. The MTF in different spacial frequencies increased after wearing OK lenses. There was no significant difference for the corneal SR before and after wearing OK lenses, and the corneal MTF decreased significantly after wearing OK lenses. (3) For the ocular, the total higher order aberration (HOA), spherical, coma and trefoil aberrations increased, and the total aberration, total lower order aberration (LOA) and defocus aberration decreased obviously except astigmatism. The corneal aberrations increased significantly after wearing OK lenses except astigmatism. For the internal optic, the total aberration, total LOA and defocus aberration decreased, and the total HOA, coma and trefoil aberration increased significantly except the astigmatism and spherical aberrations. (4) The CF and CF% of total aberration, total LOA, total HOA and coma aberrations increased, and those of astigmatism and spherical decreased at 12 months. CONCLUSIONS: Orthokeratology is effective in correcting the refractive error and improving the vision quality of juvenile myopia over the one-year follow-up period.

Differentiation of human embryonic stem cells derived mesenchymal stem cells into corneal epithelial cells after being seeded on decellularized SMILE-derived lenticules.

AIM: To evaluate the feasibility of mesenchymal stem cells (MSCs) to differentiate into corneal epithelial cells after being seeded on the decellularized small incision lenticule extraction (SMILE)-derived lenticules. METHODS: The fresh lenticules procured from patients undergoing SMILE for the correction of myopia were decellularized. The MSCs were subsequently cultivated on those denuded lenticules. The MSCs without lenticules were used as a control. The proliferation activity of the MSCs after seeding 24h was quantitatively determined with the Cell Counting Kit-8 (CCK-8) assay. Immunofluorescence staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to assess the marker expression in differentiated MSCs. RESULTS: The data showed that both fresh and decellularized lenticules could significantly promote the proliferation of MSCs, compared to that in control (P=0.02 for fresh lenticules, P=0.001 for decellularize ones, respectively). The MSCs seeded on both lenticules were positive for cytokeratin 3 (CK3) staining. The expression of CK3 increased 5-fold in MSCs seeded on fresh lenticules and 18-fold on decellularized ones, compared to that in control. There was a significant difference in the expression of CK3 in MSCs seeded on fresh and decellularized lenticules (P<0.001). The expression of CK8 and CK18 was similar in pure MSCs and MSCs seeded on fresh lenticules (P>0.05), while the expression of these markers was decreased in MSCs seeded on decellularized ones. CONCLUSION: These results suggest that the decellularized lenticules might be more suitable for MSCs to differentiate into corneal epithelial cells, which offers the prospect of a novel therapeutic modality of SMILE-derived lenticules in regenerative corneal engineering.

N-methyl-N-nitrosourea induces retinal degeneration in the rat via the inhibition of NF-κB activation.

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases characterized by the loss of photoreceptor cells through apoptosis. N-methyl-N-nitrosourea (MNU) is an alkylating toxicant that induces photoreceptor cell death resembling hereditary RP. This study aimed to investigate the role of nuclear factor κB (NF-κB) in MNU-induced photoreceptor degeneration. Adult rats received a single intraperitoneal injection of MNU (60 mg/kg bodyweight). Hematoxylin and eosin staining demonstrated progressive outer nuclear layer (ONL) loss after MNU treatment. Transmission electron microscopy revealed nuclear pyknosis, chromatin margination in the photoreceptors, increased secondary lysosomes, and lobulated retinal-pigmented epithelial cells in MNU-treated rats. Numerous photoreceptor cells in the ONL showed positive TUNEL staining and apoptosis rate peaked at 24 hours. Enhanced depth imaging spectral-domain optical coherence tomography showed ONL thinning and decreased choroid thickness. Electroretinograms showed decreased A wave amplitude that predominated in scotopic conditions. Western blot analysis showed that nuclear IκBα level increased, whereas nuclear NF-κB p65 decreased significantly in the retinas of MNU-treated rats. These findings indicate that MNU leads to selective photoreceptor degradation, and this is associated with the inhibition of NF-κB activation.