Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.

Purpose. We characterized fluorescent bone marrow cells (YFP⁺ BMCs) in the thy1-YFP mouse and determine if they promote trigeminal ganglion (TG) cell neurite growth. Methods. Excimer laser annular keratectomy was performed in thy1-YFP mice, and corneas were imaged. BMCs were harvested from femur and tibia, and the expression of surface markers on YFP⁺ BMCs was analyzed by flow cytometry. The immunosuppressive action of BMCs (YFP⁺ and YFP⁻) was evaluated in an allogenic mixed lymphocyte reaction (MLR). Neurotrophic action of BMCs (YFP⁺ and YFP⁻) was determined in compartmental and transwell cultures of dissociated TG cells. Results. Following annular keratectomy, YFP⁺ BMCs infiltrated the cornea. YFP⁺ BMCs shared surface markers (CD11b+Gr1+Ly6C+Ly6G-F4/80^low) with monocytic myeloid-derived suppressor cells (MDSCs), had similar morphology, and suppressed T-cell proliferation in allogenic MLR in a dose-dependent manner. YFP⁺ BMCs, but not YFP⁻ BMCs, significantly increased growth of TG neurites in vitro. When cultured in a transwell with TG neurites, YFP⁺ BMCs expressed neurotrophins and secreted nerve growth factor (NGF) in conditioned medium. YFP⁺ BMCs that infiltrated the cornea maintained their phenotype and actions (neuronal and immune). Conclusions. YFP⁺ BMCs in thy1-YFP mice have immunophenotypic features of MDSCs. They secrete NGF and promote neuroregeneration. Their immunosuppressive and neurotrophic actions are preserved after corneal infiltration. These findings increase our understanding of the beneficial roles played by leukocyte trafficking in the cornea and may lead to therapeutic strategies that use NGF-secreting myeloid cells to repair diseased or injured neurons.

Diquafosol is known as a purinergic P2Y2 receptor (P2Y2R) agonist that stimulates water and mucin secretion from conjunctival epithelial cells and goblet cells, leading to tear film stability in dry eye. However, its effect on corneal epithelial healing has not yet been elucidated. The aim of the present study was to evaluate the effect of diquafosol on corneal epithelial healing in vivo and on P2Y2R-related downstream signaling pathways in vitro. We administered 3% diquafosol ophthalmic solution on 3 mm-diameter epithelial defects made in rat corneas and assessed the wound closure over time. Corneal epithelial healing was significantly accelerated in diquafosol-treated eyes compared to control eyes at 12 and 24 h. During wound healing, P2Y2R staining appeared stronger in the re-epithelized margin near the wound defect. To evaluate whether diquafosol stimulates epidermal growth factor receptor/extracellular-signal-regulated kinase (EGFR/ERK)-related cell proliferation and migration, simian virus 40-transfected human corneal epithelial (THCE) cells were used for in vitro experiments. Cell proliferation was accelerated by diquafosol at concentrations from 20 to 200 μM during 48 h, but inhibited at concentrations over 2000 μM. The intracellular calcium ([Ca(2+)]i) elevation was measured in diquafosol (100 μM)-stimulated cells using Fluo-4/AM ([Ca(2+)]i indicator). [Ca(2+)]i elevation was observed in diquafosol-stimulated cells regardless of the presence of calcium in media, and suramin pretreatment inhibited the calcium response. The effect of diquafosol on phosphorylation of EGFR, ERK and Akt, and cell migration was determined by western blotting and in vitro cell migration assay. Diquafosol induced phosphorylation of EGFR at 2 min post-stimulation, and phosphorylation of ERK at 5 min post-stimulation. Phosphorylation of ERK was attenuated in cells pretreated with suramin or BAPTA/AM ([Ca(2+)]i chelator), and partially with AG1478 (EGFR inhibitor). Likewise, diquafosol-treated cells showed acceleration of gap closure in cell migration assay, which was inhibited by suramin, BAPTA/AM, AG1478, and U0126 (MEK inhibitor). These studies demonstrate that diquafosol is effective in promoting corneal epithelial wound healing and that this effect may result from ERK-stimulated cell proliferation and migration via P2Y2R-mediated [Ca(2+)]i elevation.

Posterior subtenon injection (PSTI) of triamcinolone acetonide (TA) is one of the delivery methods for the treatment of posterior uveitis, diabetic macular edema, and cystoid macular edema secondary to retinal vein occlusions. The aim of this investigation was to assess the rates of various complications associated with PSTI and to determine which factors are associated with the development of complications. This investigation was a retrospective interventional case series, and one retinal specialist from 2005 to 2007 conducted all of the procedures. Patients were followed up for a mean time of 11.9 +/- 5.4 months after receiving 40 mg (1.0 mL) of nonfiltered TA and all complications associated with the injection procedure or with TA itself were noted. A total of 159 eyes in 158 patients were treated by PSTI of TA. Of 159 eyes, 145 eyes (91.2%) were injected once, 13 eyes (8.2%) were injected twice, and one eye (0.6%) was injected three times. The mean age of the 158 patients was 61.6 +/- 9.5 years. Eighteen eyes (11.3%) required glaucoma medication due to increased intraocular pressure (IOP) after injection. In addition, cataracts in three eyes (2.1%) progressed with biomicroscopic findings, as compared with the fellow eyes. There were no cases of mechanical injury, infection or ulceration of any part of eye, and eyelid complications. A conjunctival cyst at the injection site developed in one eye. In this study, PSTI of TA resulted in no severe complications such as endophthalmitis or retinal detachment, and a relatively less risk of IOP complications and cataract progression. PSTI of TA is an extremely safe procedure and can be repeatedly applied to an eye.

To compare the efficacy of microincision and small-incision coaxial phacoemulsification in treating hard cataracts using different ultrasound power modes. Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea. Randomized clinical trial. Eyes with hard cataract were randomized to have an initial incision of 1.80 mm, 2.20 mm, or 2.75 mm. The eyes in each group were equally randomized to treatment with burst, pulse, or continuous mode. Ultrasound time (UST), mean cumulative dissipated energy (CDE), corrected distance visual acuity (CDVA), surgically induced corneal astigmatism, incisional and central corneal thickness (CCT), and endothelial cell counts were evaluated. The study enrolled 180 eyes, 60 in each group. Two months postoperatively, there were no statistically significant differences in UST, CDE, CDVA, CCT, or percentage endothelial cell loss between the 3 incision groups. The 2.75 mm incision induced more astigmatism at 2 months and less incisional corneal edema at 1 week than the 1.80 mm or 2.20 mm incision (P<.05). The UST, CDE, incisional corneal thickness, and CCT at 1 week and the percentage endothelial cell loss at 2 months with continuous mode were statistically significantly higher than with pulse mode and burst mode in all 3 incision groups (P<.05). Phacoemulsification using microincisions may be as safe and effective as the conventional small incision for hard cataract. The intraoperative energy use and ocular damage was less with the pulse and burst modes than with the continuous mode. No author has a financial or proprietary interest in any material or method mentioned.