Ocular biometric characteristics of Han ethnicity in Tianjin and Uyghur ethnicity in Xinjiang undergoing cataract surgery.

AIM: To analyze and compare the differences among ocular biometric parameters in Han and Uyghur populations undergoing cataract surgery. METHODS: In this hospital-based prospective study, 410 patients undergoing cataract surgery (226 Han patients in Tianjin and 184 Uyghur patients in Xinjiang) were enrolled. The differences in axial length (AL), anterior chamber depth (ACD), keratometry [steep K (Ks) and flat K (Kf)], and corneal astigmatism (CA) measured using IOL Master 700 were compared between Han and Uyghur patients. RESULTS: The average age of Han patients was higher than that of Uyghur patients (70.22±8.54 vs 63.04±9.56y, P<0.001). After adjusting for age factors, Han patients had longer AL (23.51±1.05 vs 22.86±0.92 mm, P<0.001), deeper ACD (3.06±0.44 vs 2.97±0.37 mm, P=0.001), greater Kf (43.95±1.40 vs 43.42±1.69 D, P=0.001), steeper Ks (45.00±1.47 vs 44.26±1.71 D, P=0.001), and higher CA (1.04±0.68 vs 0.79±0.65, P=0.025) than Uyghur patients. Intra-ethnic male patients had longer AL, deeper ACD, and lower keratometry than female patients; however, CA between the sexes was almost similar. In the correlation analysis, we observed a positive correlation between AL and ACD in patients of both ethnicities (rHan =0.48, rUyghur =0.44, P<0.001), while AL was negatively correlated with Kf (rHan =-0.42, rUyghur =-0.64, P<0.001) and Ks (rHan =-0.38, rUyghur =-0.66, P<0.001). Additionally, Kf was positively correlated with Ks (rHan =0.89, rUyghur =0.93, P<0.001). CONCLUSION: There are differences in ocular biometric parameters between individuals of Han ethnicity in Tianjin and those of Uyghur ethnicity in Xinjiang undergoing cataract surgery. These ethnic variances can enhance our understanding of ocular diseases related to these parameters and provide guidance for surgical procedures.

INOS ablation promotes corneal wound healing via activation of Akt signaling.

Corneal injury leads to impaired normal structure of the cornea. Improving the wound healing process in epithelial cells significantly contributes to ocular damage treatments. Here, we aimed to investigate the potential mechanisms of nitric oxide (NO) and its mediator, inducible nitric oxide synthase (iNOS), in the process of corneal wound healing. We established a corneal injury model of iNOS-/- mice, and treated human corneal epithelial cell lines (HCE-2) with the iNOS inhibitor L-INL, with or without NO replenishment by supplying sodium nitroferricyanide dihydrate (SNP). Our findings showed that inhibition of NO/iNOS accelerated corneal repair, enhanced uPAR (a receptor protein indicating the migration ability), and improved epithelial cell migration. Furthermore, NO/iNOS ablation activated Akt phosphorylation, reduced neutrophil marker protein MPO expression, and downregulated the transcription of inflammation cytokines CXCL-1, CXCL-2, IL-1ß, IL-6, and TNF-α. However, the protective effects of NO/iNOS inhibition are significantly reduced by NO replenishment when treated with SNP. Therefore, we confirmed that inhibiting NO/iNOS improved the corneal wound healing by facilitating epithelial cell migration and reducing inflammatory reactions, which might be related to the activation of the Akt signaling pathway.

Characteristics of the ocular surface in neurotrophic keratitis induced by trigeminal nerve injury following neurosurgery.

PURPOSE: To analyse and quantify ocular surface parameters in patients with unilateral neurotrophic keratitis (NK) induced by trigeminal nerve injury post-neurosurgery. METHODS: The study included 26 unilateral NK patients who had undergone neurosurgery, and 20 matched normal controls. Demographic and clinical characteristics of all participants were collected and analysed. Slit-lamp examination, Cochet-Bonnet aesthesiometry, Keratograph 5 M, and LipiView interferometer were performed on both eyes of 17 mild NK patients. For nine moderate/severe NK patients, sub-basal nerve density was measured by in vivo confocal microscopy. RESULTS: Of the 26 patients, nine had acoustic neuroma, nine had trigeminal neuralgia, and eight had neoplasms. Facial nerve paralysis was observed in one of the 17 mild NK eyes (5.9%) and seven of the nine moderate/severe NK eyes (77.8%). Compared to contralateral and normal control eyes, 26 NK eyes showed significantly reduced sensitivity in five corneal regions (P < 0.05). Corneal sensitivity in moderate/severe NK eyes was significantly lower than in mild NK eyes (P < 0.05). Moderate/severe NK eyes had poor visual acuity, and their sub-basal nerve density was lower than that of the controls. The onset of the moderate/severe NK was from 0.5 to 24 months (median [Q1, Q3], 1 [0.5, 2.5] months) after neurosurgery. For the mild NK eyes, the number of total blinks, the first non-invasive tear breakup time (NITBUT) and average NITBUT were significantly lower than contralateral and normal control eyes (P < 0.05), and the number of partial blinks and partial blinking rate were significantly higher than the other two control groups (P < 0.05). CONCLUSIONS: Patients with NK induced by trigeminal nerve injury following neurosurgery had decreased corneal sensitivity to various degrees accompanied by increased partial blinks and shortened NITBUT. The severity of NK is related to the severity of the corneal sensory impairment. Facial nerve paralysis can worsen the clinical progression of NK. Trial registration Chinese Clinical Trial Registry (ChiCTR2100044068, Date of Registration: March 9, 2021).

MSC-Derived Small Extracellular Vesicles Attenuate Autoimmune Dacryoadenitis by Promoting M2 Macrophage Polarization and Inducing Tregs via miR-100-5p.

Background: Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied. Methods: Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores. Quantitative real-time PCR (Q-PCR), western blot and flow cytometry were performed to evaluate the immunomodulatory effects of hUC-MSC-sEVs on macrophages and T regulatory cells (Tregs) both in vivo and in vitro, and the in vitro T cell proliferation was detected by Bromodeoxyuridine (BrdU) assay. In addition, high expression of miR-100-5p in hUC-MSC-sEVs was identified by Q-PCR, and the functional role of sEVs-miR-100-5p on macrophages was explored by a series of co-culture experiments using sEVs derived from hUC-MSCs transfected with miR-100-5p inhibitor. Results: We firstly demonstrated that hUC-MSC-sEVs had the preventive and therapeutical effects on rabbit autoimmune dacryoadenitis, an animal model of Sjögren's syndrome (SS) dry eye. Further investigation revealed that hUC-MSC-sEVs administration effectively elicited macrophages into an anti-inflammatory M2 phenotype and elevated the proportion of Tregs both in vivo and in vitro, which contributed to reduced inflammation and improved tissue damage. Importantly, hUC-MSC-sEVs-educated macrophages with M2-like phenotype exhibited strong capacity to inhibit CD4+ T cell proliferation and promote Treg generation in vitro. Mechanistically, miR-100-5p was highly enriched in hUC-MSC-sEVs, and knockdown of miR-100-5p in hUC-MSC-sEVs partially blunted the promotion of hUC-MSC-sEVs on M2 macrophage polarization and even attenuated the effect of hUC-MSC-sEVs-educated macrophages on T cell suppression and Treg expansion. Conclusion: Our data indicated that hUC-MSC-sEVs alleviated autoimmune dacryoadenitis by promoting M2 macrophage polarization and Treg generation possibly through shuttling miR-100-5p. This study sheds new light on the application of MSC-sEVs as a promising therapeutic method for SS dry eye.

Posterior scleral reinforcement for the treatment of myopic traction maculopathy.

BACKGROUND: This study aimed to investigate the clinical effectiveness of posterior scleral reinforcement(PSR) for the treatment of myopic traction maculopathy (MTM). METHODS: This was a prospective study of 32 eyes from 20 patients with MTM treated with PSR using genipin-cross-linked donor sclera. The length of the scleral strip used for the surgery was designed to be 1.5-times the axial length of the eye, whereas its width was 0.4-times the axial length of the eye. The optical coherence tomography images, spherical equivalent of refractive error, axial length, best corrected visual acuity, electroretinogram findings, and intraocular pressure of the patients were assessed postoperatively. RESULTS: The mean duration of follow-up was 17.80 ± 8.74 months. The differences between the spherical equivalent of refractive error, best corrected visual acuity, axial length, and electroretinogram findings recorded preoperatively and those measured postoperatively were statistically significant (p < 0.05). The final reduction in axial length was 1.64 ± 0.85 mm. At the end of the follow-up, optical coherence tomography showed essential foveal reattachment in 30 eyes (93.75%), partial reattachment in two eyes (6.25%), and closure of macular holes in seven eyes (77.78%). No retinal detachment, vitreous haemorrhage, or other serious complications occurred following the surgery. CONCLUSIONS: Posterior scleral reinforcement with genipin-cross-linked sclera showed safe and effective outcomes for the treatment of MTM during a follow-up period of at least one year. TRIAL REGISTRATION: 11\12\2018, ChiCTR1800020012 .

Changes in asphericity of anterior and posterior corneal surfaces for mild-moderate and high myopia after topography-guided FS-LASIK.

PURPOSE: To compare changes in asphericity of anterior and posterior corneal surfaces for different myopia patients after corneal topography-guided femtosecond-assisted laser in situ keratomileuses (FS-LASIK), and to analyze correlations between asphericity of corneal surfaces and preoperative spherical equivalence (SEQ). METHODS: In this prospective study, 59 patients who underwent corneal topography-guided FS-LASIK surgery were enrolled and divided into the mild-moderate myopia group (67 eyes) and the high myopia group (44 eyes). Postoperative follow-ups were performed at 1, 3, and 6 months. Postoperative changes in aspherical coefficient (Q values), corneal higher-order aberrations (HOAs), and spherical aberrations (Z40) were compared between the two groups. Relevance between Q value changes and SEQ, HOAs, and Z40 as well as between SEQ and changes of HOAs and Z40 was analyzed. RESULTS: There was a significant increase in Q values of the anterior (each diameter) and posterior (6-8 mm) corneal surface in both groups than before surgery (P < 0.001). Q values of corneal anterior (each diameter) and posterior (7-9 mm) surface in the high group were considerably larger than the mild-moderate group (P < 0.05). Corneal anterior surface HOAs and Z40 values in the high group largely exceeded those of the mild-moderate group (P < 0.001). The preoperative SEQ was linearly correlated with postoperative anterior Q change (ΔQ), HOAs change (ΔHOAs), and spherical aberration change (ΔZ40). CONCLUSION: The changes of corneal asphericity in patients with high myopia were greater than mild-moderate myopia, with more corneal HOAs and Z40 introduced when corneal topography-guided FS-LASIK was conducted.

Comparative study of objective visual quality between FS-LASIK and SMART in myopia.

AIM: To compare the changes in the objective visual quality of patients with low and moderate myopia postoperatively after transepithelial photorefractive keratectomy using the smart pulse technology (SMART) and femtosecond laser in situ keratomileusis (FS-LASIK). METHODS: Corneal higher-order aberrations (HOAs), horizontal coma, vertical coma and spherical aberration were measured using Pentacam, and cutoff for modulation transfer function (MTF cutoff), objective scatter index (OSI) and Strehl ratio (SR) was measured using an optical quality analysis system (OQAS-II), before and after operation at 1, 3, and 6mo, and data were analyzed by repeated measurement two-way analysis of variance. RESULTS: The difference in uncorrected distance visual acuity between SMART and FS-LASIK was statistically significant only 1wk postoperatively. Approximately 86.36% and 80.69% of patients with spherical equivalent (SE) in ±0.50 D were observed in the SMART and FS-LASIK groups, respectively. No significant difference was observed in SE between the two groups (P=0.509). The HOAs increased postoperatively compared with those before surgery in both groups (P<0.05). No significant difference in HOA, corneal horizontal coma, spherical aberration, ΔHOA, Δhorizontal coma, and Δspherical aberration were observed between the two group (P>0.05). Corneal vertical coma and Δcorneal vertical coma in the FS-LASIK group were higher than those in the SMART group (P<0.05). The OSI of both groups at 1mo after surgery was higher than that before surgery (P<0.05). At 3 and 6mo postoperatively, the OSI in the FS-LASIK group was slightly higher than that in the SMART group (P=0.040 and 0.047, respectively). At 6mo after surgery, the MTF cutoff was statistically significant different between the two groups (P=0.026). No significant difference in SR between the FS-LASIK and SMART groups was observed at 1, 3, and 6mo postoperatively (P>0.05). CONCLUSION: The HOAs increase and visual quality is delayed in both groups postoperatively, and the long-term objective visual quality after SMART is slightly better than that after FS-LASIK.

Analysis of Tear Function Outcomes following Collagen Cross-Linking Treatment in Ectatic Corneas.

Purpose: To analyze tear function outcomes following collagen cross-linking (CXL) treatment in ectatic corneas. Methods: Fifty-seven eyes of 34 patients were included, and patients with keratoconus who underwent epithelium-on (epi-on) or epithelium-off (epi-off) CXL were evaluated. The following tests were performed preoperatively and at 1, 3, 6, and 12 months postoperatively: best-corrected visual acuity (BCVA), maximum keratometry value (Kmax), ocular surface disease index (OSDI) questionnaire, slit-lamp examination, tear meniscus height, first noninvasive Keratograph breakup time (1st NIKBUT), average NIKBUT, and bulbar redness. Results: BCVA improved in both epi-on and epi-off groups at most follow-up points, but was not significantly different between groups. At 12-month follow-up, Kmax in the epi-on and epi-off groups improved after CXL, but there was no significant difference between the groups. The OSDI in both groups decreased after operation compared with before surgery, and there was no significant difference between the two groups. Comparing the two groups, only the change in the tear meniscus height at 6 months postoperatively was statistically significant, and the pre- and postoperative values of the two groups were within the normal range (>0.20 mm). The change was small and had no clinical significance. There was no change in the 1st NIKBUT and average NIKBUT between the epi-on and epi-off groups. A change in bulbar redness was significantly better in the epi-off group than in the epi-on group at 3 months postoperatively. Comparing the effects at 1 year postoperatively, both groups had positive results in OSDI, NIKBUT, tear meniscus height, and bulbar redness. Conclusion: Both epi-on and epi-off CXL can control the progression of keratoconus, although epi-off CXL is more effective. Both methods have a positive effect on dry eye, which can improve the condition of the tear film and reduce dry eye symptoms in patients with keratoconus.

Corneal Asphericity and Higher-Order Aberrations after FS-LASIK and Trans-PRK for Myopia.

OBJECTIVE: To compare the corneal asphericity and higher-order aberrations (HOAs) of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) with Smart Pulse Technology (SPT) assisted transepithelial photorefractive keratectomy (Trans-PRK) for myopia and myopic astigmatism correction. METHODS: This prospective study analyzed 88 eyes of 44 patients treated with FS-LASIK and 64 eyes of 32 patients treated with Trans-PRK. All eyes had low to moderate myopia with or without astigmatism (spherical equivalent (SE) <-6.00 diopters). The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), SE, asphericity (Q value) of the anterior corneal surface, index of surface variance (ISV), corneal higher-order aberrations (HOAs), vertical coma (Z3 -1), horizontal coma (Z3 1), and spherical aberration (Z 4 0) over a 6 mm diameter central corneal zone diameter were evaluated preoperatively and 1, 3, and 6 months postoperatively. RESULTS: At 6 months, the UDVA and SE were -0.14 ± 0.06 and 0.33 ± 0.33D in FS-LASIK and -0.15 ± 0.06 and 0.35 ± 0.37D in Trans-PRK. There was no difference between the two groups in the postoperative UDVA and SE (P > 0.05). After FS-LASIK and Trans-PRK, the Q values in the 6, 7, 8, and 9 mm zones and ISV of the anterior corneal surface significantly increased (P < 0.001). At 1, 3, and 6 months after surgery, corneal HOA, Z3 -1, Z 3 1, and Z 4 0 in both groups were significantly increased compared with those before surgery, with statistically significant differences (P < 0.001). At 1, 3, and 6 months after surgery, the Z3 -1 of the Trans-PRK group was significantly lower than that of the FS-LASIK group (P < 0.001). ΔHOA and ΔZ4 0 were dramatically correlated with the ΔQ value for both FS-LASIK and Trans-PRK procedures. The ΔQ was significantly correlated with the preoperative SE, AD, and AD/CCT after both two procedures (all P < 0.001). CONCLUSIONS: Both FS-LASIK and Trans-PRK caused the anterior corneal surface to become flatter, and the morphology of the corneal surface was irregular. Corneal HOAs were significantly increased after the two procedures. Trans-PRK using SPT introduced less corneal vertical coma than FS-LASIK. Corneal asphericity changes contributed to the corneal aberrations changes following FS-LASIK and Trans-PRK.

Aberrantly expressed GFRα-1/RET in patients with lacrimal adenoid cystic carcinoma is associated with high recurrence risk: a retrospective study of 51 LACC cases.

Objective: Because of the poor prognosis of lacrimal adenoid cystic carcinoma (LACC), we aimed to investigate the effects of perineural invasion (PNI) and consequent aberrations in GDNF/GFRα-1/RET protein expression on LACC recurrence. Methods: Clinicopathological data for 51 histologically confirmed patients with LACC enrolled between 2001 and 2017 were retrospectively analyzed. Hematoxylin and eosin staining was applied to assess PNI. Tissue-based immunohistochemistry (IHC) detection of GDNF, GFRα-1, and RET proteins was performed on LACC formalin-fixed, paraffin-embedded specimens. We generated semi-quantitative data of the IHC results and compared them with the clinicopathological data for the 51 patients. Results: Of the 51 patients, 19 (37.3%) were PNI positive. Recurrence was more common for LACC with than without PNI (73.7% vs. 37.5%, P = 0.01). GDNF, GFRα-1, and RET proteins were expressed in 62.7%, 62.7%, and 54.9% of the 51 patients with LACC, respectively. The expression of all 3 proteins was more common in patients with than without PNI. In agreement with previous findings, PNI-associated GFRα-1 and RET positivity, as detected by IHC, remained significantly associated with recurrence, whereas GDNF expression, as detected by IHC, was not correlated with LACC recurrence. Specifically, patients with concurrent GFRα-1 and RET expression may have a high risk of PNI (89.5% positivity rate) and recurrence (84.2% positivity rate). Conclusions: PNI may contribute to LACC recurrence. The concurrent expression of GFRα-1 and RET proteins, as detected by IHC, may potentially be associated with LACC PNI and recurrence.

Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype.

Mesenchymal stem cells (MSCs) exhibit beneficial effects on autoimmune dacryoadenitis. However, the underlying mechanisms are not fully understood. In this study, we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on rabbit autoimmune dacryoadenitis, an animal model of Sjögren's syndrome (SS) dry eye, and explored whether the effects of MSCs were related to their modulation on macrophage polarization. We have showed that systemic infusion of hUC-MSCs after disease onset efficiently diminished the chronic inflammation in diseased LGs and improved the clinical symptoms. Further analysis revealed that hUC-MSC treatment significantly inhibited the expression of pro-inflammatory M1 macrophage markers iNOS, TNF-α and IL-6, and promoted the expression of anti-inflammatory M2 macrophage markers Arg1, CD206, IL-10, IL-4 and TGF-ß in LGs. Mechanistically, hUC-MSCs activated AKT pathway in macrophages, resulting in upregulation of M2-associated molecule Arg1, which was partly abolished by PI3K inhibitor, LY294002. Together, our data indicated that hUC-MSCs can skew macrophages into an M2 phenotype via affecting AKT pathway. These data may provide a new insight into the mechanisms of hUC-MSCs in the therapy of SS dry eye.

miR-223-3p promotes autoreactive Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression.

Pathogenic T helper (Th)17 cells are key mediators of autoimmune diseases such as uveitis and its animal model, experimental autoimmune uveitis (EAU). However, the contribution of microRNAs (miRs) to the intrinsic control of pathogenic Th17 cells in EAU remains largely unknown. Here, we have reported that miR-223-3p was significantly up-regulated in interphotoreceptor retinoid-binding protein-specific Th17 cells, and its expression was enhanced by IL-23-signal transducer and activator of transcription 3 signaling. Knockdown of miR-223-3p decreased the pathogenicity of Th17 cells in a T-cell transfer model of EAU. Mechanistic studies showed that miR-223-3p directly repressed the expression of forkhead box O3 (FOXO3), and FOXO3 negatively regulated pathogenic Th17 cell responses partially via suppression of IL-23 receptor expression. Thus, our results reveal an important role for miR-223-3p in autoreactive Th17 cell responses and suggest a potential therapeutic avenue for uveitis.-Wei, Y., Chen, S., Sun, D., Li, X., Wei, R., Li, X., Nian, H. miR-223-3p promotes autoreactive Th17 cell responses in experimental autoimmune uveitis (EAU) by inhibiting transcription factor FOXO3 expression.

The prevalence of vision impairment and refractive error in 3654 first year students at Tianjin Medical University.

AIM: To determine the prevalence of vision impairment (VI) and refractive error in first year university students at the Tianjin Medical University. METHODS: This is a cross-sectional observational cohort study of VI and refractive error among first year university students at the Tianjin Medical University. The first year university students were involved in this study and were given a detailed questionnaire including age, birth date, and spectacle wearing history. A standardized ophthalmologic examination including visual acuity (VA), slit-lamp examination, non-cycloplegic auto-refraction, objective refraction, fundus photography, and examination of their spectacles were recorded. RESULTS: A total of 3654 participants were included in this study. Totally 3436 (94.03%) individuals had VI in this population. Totally 150 (4.10%) individuals had VI due to ocular disease, including amblyopia, congenital cataract, retinal atrophy or degeneration, strabismus, congenital nystagmus, refractive surgery orthokeratology. Totally 3286 (89.93%) subjects had VI due to refractive error. Only 218 (5.97%) students were emmetropia. Moreover, refractive error was the main cause for the VI (95.63%). Totally 3242 (92.52%) students were myopia and the prevalence of mild, moderate, and high myopia subgroup was 27.05%, 44.35%, and 21.26% respectively. Totally 44 (1.29%) subjects were hyperopic. The rates of uncorrected visual acuity (UCVA), presenting visual acuity (PVA) and best corrected visual acuity (BCVA) which better than 20/20 in both eyes were 5.65%, 22.32% and 82.13% respectively. The rates of correction, under correction and well correction in myopia subjects were 82.73%, 84.39% and 15.61%, respectively. CONCLUSION: We present a high prevalence of refractive errors and high rates of under correction refractive error among first year university students. These results may help to promote vision protection work in young adults.

Interface fluid syndrome: A potential lifelong complication after LASIK. A case report.

PURPOSE: To describe a case of interface fluid formation caused by uncontrollable intraocular pressure (IOP) 16 years after laser-assisted in situ keratomileusis (LASIK) surgery secondary to Posner Schlossman Syndrome (PSS). OBSERVATIONS: After trabeculectomy operation, IOP of the operative eye was back to normal, and the interface fluid refluxed over time. CONCLUSIONS: and importance: Interface Fluid Syndrome can be a potential lifelong complication after LASIK surgery. PSS patients post-LASIK require early IOP control.

Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R.

BACKGROUND/AIMS: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). METHODS: Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. RESULTS: Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested partial rescue of functional defects by α-MSH in diabetic retinas; and H&E staining revealed significantly increased thickness of all layers in α-MSH-treated diabetic retinas. Mechanistically, α-MSH corrected aberrant transcript and protein expression of pro-inflammatory factor and tight junction genes in the diseased retinas; moreover, it prevented abnormal changes in TEER and permeability in HG-stimulated RF6A cells, and this anti-hyperpermeability was abolished by a universal MCR blocker or an antagonist specific to MC4R. CONCLUSIONS: This study showed previously undescribed protective effects of α-MSH on inhibiting BRB breakdown and vascular leakage, improving electrophysiological functions and morphology in early diabetic retinas, which may be due to its down-regulating pro-inflammatory factors and augmenting tight junctions. α-MSH acts predominantly on MC4R to antagonize hyperpermeability in retinal microvessel endothelial cells.

Mesenchymal stem cells for treating autoimmune dacryoadenitis.

Autoimmune dacryoadenitis, such as Sjögren syndrome, comprises multifactorial and complex diseases. Inflammation of the lacrimal gland plays a key role in the pathogenesis of diseases. Unfortunately, current treatment strategies, including artificial tears, anti-inflammatory drugs, punctual occlusion, and immunosuppressive drugs, are only palliative, and long-term administration of these strategies is associated with adverse effects that limit their utility. Hence, an effective and safe treatment for autoimmune dacryoadenitis is urgently needed. Mesenchymal stem cells (MSCs) have emerged as a promising tool for treating autoimmune dacryoadenitis, owing to their immunosuppressive properties, tissue repair functions, and powerful differentiation capabilities. A large number of studies have focused on the effect of MSCs on autoimmune diseases, such as autoimmune uveitis, inflammatory bowel disease, and collagen-induced arthritis, but few studies have, to date, unequivocally established the efficacy of MSCs for treating autoimmune dacryoadenitis. In this review, we discuss recent advances in MSC treatment for autoimmune dacryoadenitis.

Comparison of fibrin glue and Vicryl sutures in conjunctival autografting for pterygium surgery.

PURPOSE: To compare clinical parameters and the tear levels of inflammatory cytokines between pterygium surgery using sutures or fibrin glue. METHODS: Fifty-six patients with primary pterygium were divided into the suture group and the glue group, in which the autograft was secured with 10-0 Vicryl sutures and fibrin glue, respectively. A questionnaire, slit-lamp examination, Schirmer test, and visual acuity test were performed in all participants. Real-time quantitative PCR (q-PCR) was used to analyze the expression of genes in pterygium and healthy conjunctival tissues. Based on the qPCR results and literature reports, five inflammatory cytokines, including hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2), transforming growth factor-ß1 (TGF-ß1), matrix metalloproteinase 2 (MMP2), and tumor necrosis factor-α (TNF-α), were selected, and their protein levels were measured with enzyme-linked immunosorbent assay (ELISA) in patient tears before surgery as well as at postoperative day 1, 7, and 30. RESULTS: There are 28 patients in either the suture or the glue group. The average duration of surgery was 20.17 ± 3.23 min for the glue group and 32.42 ± 4.47 min for the suture group (p = 0.000). Visual acuity in both groups was improved (p = 0.002) after the surgical procedures. There were more symptoms in the suture group than in the glue group at postoperative day 7 (p = 0.002). Postoperative symptoms disappeared in both groups at 1 month after surgery. Recurrence was observed in one case in the glue group and in two cases in the suture group at the 6 month postoperative follow-up (p = 0.714). In comparison to the preoperative levels (4.33 ± 0.43 ng/ml for the suture group; 4.20 ± 0.26 ng/ml for the glue group), the levels of TNF-α in tears increased in the suture group (5.02 ± 0.49 ng/ml, p = 0.016) and decreased in the glue group (3.84 ± 0.35 ng/ml, p = 0.052) on postoperative day 1. The glue treatment induced higher HGF production (4.78 ± 1.25 ng/ml) than the suture treatment (3.04 ± 1.18 ng/ml) at postoperative day 1 (p = 0.020). Higher levels of TGF-ß1 in the glue group were detected at postoperative day 1 (3.71 ± 0.18 ng/ml) and postoperative day 30 (4.50 ± 0.51 ng/ml), compared to those in the suture group, respectively (2.74 ± 0.21 ng/ml, p = 0.000 for day 1; 3.36 ± 0.96 ng/ml, p = 0.017 for postoperative day 30). CONCLUSIONS: Fibrin glue is effective and safe for attaching conjunctival autografts with an easy surgical procedure, shortened operating time, and less postoperative discomfort. In the early postoperative period, the protein expression of inflammatory cytokines implicates that fibrin glue may induce accelerated healing and subdued inflammation on the ocular surface compared to sutures.

Clinical evaluation of surgery-induced astigmatism in cataract surgery using 2.2 mm or 1.8 mm clear corneal micro-incisions.

AIM: To evaluate corneal astigmatism after phacoemulsification using 2.2 mm or 1.8 mm clear corneal micro-incisions and its effects on visual function. METHODS: Sixty cases (60 eyes) with cataract were randomly divided into groups A (n=30) and B (n=30) respectively underwent 2.2 mm and 1.8 mm clear corneal tunnel incision phacoemulsification combined with folding intraocular lens implantation from the time direction of 11:00. On day 1 and at 1, 4, and 6wk after operation, patients' vision was measured and both the corneal curvature and corneal thickness (CT) were recorded using Pentacam. RESULTS: The measured surgery-induced astigmatism (SIA) in both groups A and B peaked on day 1 after operation, and then gradually decreased and eventually stabilized in week 4. No statistically significant difference was found in corneal astigmatism between two groups (P>0.05). The measured corneal astigmatism at 4wk and 6wk postoperatively were 0.28±0.09 D and 0.27±0.10 D for groups A and 0.27±0.09 D and 0.25±0.10 D for groups B without statistically significant difference (P>0.05). In addition, no significant differences in visual acuity and CT were found between groups A and B before or after operation. CONCLUSION: Both 2.2 mm and 1.8 mm micro-incision cataract surgeries result in relatively small SIA with no difference in visual function and corneal astigmatism between two surgery approaches. Thus, the two types of surgical systems are safe and efficient for cataract treatment, by which satisfactory uncorrected visual acuity can be regained early postoperatively.

Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a Rabbit Model of Induced Autoimmune Dacryoadenitis.

PURPOSE: To investigate the immunoregulatory roles of adipose-derived mesenchymal stem cells (ADSCs) in autoimmune dacryoadenitis. METHODS: Rabbits were treated with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after injection of activated peripheral blood lymphocytes, and clinical scores were determined by assessing tear production, break-up time, and fluorescein and hematoxylin and eosin staining. Inflammatory response was determined by measuring the expression of different mediators of inflammation in the lacrimal glands. The Th1/Th17-mediated autoreactive responses were evaluated by determining the proliferative response and the expression of cytokine genes and the lineage-determining transcription factors. The frequency of regulatory T cells (Tregs) was also examined. RESULTS: The ADSC-treated rabbits showed decreased autoimmune responses, and the secretory function of their lacrimal gland was restored significantly. Treatment with ADSCs downregulated the Th1 and Th17 responses but enhanced Tregs function. In addition, ADSC treatment noticeably suppressed the expression of matrix metalloproteinase (MMP)-9, MPP-2, IL-1ß, and IL-6, whereas it enhanced the expression of the anti-inflammatory cytokine IL-10. CONCLUSIONS: Our results demonstrated that ADSC administration efficiently ameliorates autoimmune dacryoadenitis mainly via modulating Th1/Th17 responses.

Interleukin-1ß and tumour necrosis factor-α levels in conjunctiva of diabetic patients with symptomatic moderate dry eye: case-control study.

OBJECTIVES: To compare expression of interleukin (IL)-1ß and tumour necrosis factor (TNF)-α in the conjunctiva of diabetic and non-diabetic patients with symptomatic moderate dry eye. SETTING AND PARTICIPANTS: Nineteen diabetic patients with dry eye, 15 non-diabetic patients with dry eye and 14 diabetic patients without dry eye were recruited. The relative expression of IL-1ß and TNF-α in conjunctival impression cytology (CIC) specimens was evaluated using immunofluorescent staining and in conjunctival biopsy specimens using immunohistochemical staining. RESULTS: The diabetic dry eye group showed significantly higher grades of metaplasia than the non-diabetic dry eye and diabetic without dry eye groups (both p<0.05). There was no significant difference in the concentration of IL-1ß and TNF-α in CIC specimens between the three groups (p=0.504 and p=0.310, respectively). The mean levels of IL-1ß and TNF-α in conjunctival biopsy specimens from the diabetic dry eye group was significantly increased compared with the non-diabetic dry eye and diabetic without dry eye groups (p=0.002, p<0.001; p=0.001, p<0.001, respectively). Interestingly, IL-1ß- and TNF-α-positive cells were mainly located in the basal layer of the conjunctival epithelium, and rarely seen in the apical conjunctival epithelium in the three groups. The levels of both IL-1ß and TNF-α did not correlate with conjunctival squamous metaplasia grades. CONCLUSIONS: Levels of IL-1ß and TNF-α in conjunctival biopsy specimens were increased in diabetic patients with dry eye, while levels of IL-1ß and TNF-α in apical conjunctival epithelium were similar in the CIC specimens. These findings suggest that the inflammatory response is not limited to the surface of conjunctival epithelial cells, and is more serious in the basal layer of the epithelium, which may play an important role in the pathogenesis of dry eye in diabetic patients.