Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage.

Recent studies have demonstrated that mesenchymal stem cells (MSCs) can donate mitochondria to airway epithelial cells and rescue mitochondrial damage in lung injury. We sought to determine whether MSCs could donate mitochondria and protect against oxidative stress-induced mitochondrial dysfunction in the cornea. Co-culturing of MSCs and corneal epithelial cells (CECs) indicated that the efficiency of mitochondrial transfer from MSCs to CECs was enhanced by Rotenone (Rot)-induced oxidative stress. The efficient mitochondrial transfer was associated with increased formation of tunneling nanotubes (TNTs) between MSCs and CECs, tubular connections that allowed direct intercellular communication. Separation of MSCs and CECs by a transwell culture system revealed no mitochiondrial transfer from MSCs to CECs and mitochondrial function was impaired when CECs were exposed to Rot challenge. CECs with or without mitochondrial transfer from MSCs displayed a distinct survival capacity and mitochondrial oxygen consumption rate. Mechanistically, increased filopodia outgrowth in CECs for TNT formation was associated with oxidative inflammation-activated NFκB/TNFαip2 signaling pathways that could be attenuated by reactive oxygen species scavenger N-acetylcysteine (NAC) treatment. Furthermore, MSCs grown on a decellularized porcine corneal scaffold were transplanted onto an alkali-injured eye in a rabbit model. Enhanced corneal wound healing was evident following healthy MSC scaffold transplantation. And transferred mitochondria was detected in corneal epithelium. In conclusion, mitochondrial transfer from MSCs provides novel protection for the cornea against oxidative stress-induced mitochondrial damage. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.

Systematic screening for diabetic retinopathy (DR) in Hong Kong: prevalence of DR and visual impairment among diabetic population.

PURPOSE: To determine the prevalence of diabetic retinopathy (DR), sight threatening DR (STDR), visual impairment and other eye diseases in a systematic DR screening programme among primary care Chinese patients with diabetes mellitus (DM) in Hong Kong. METHODS: Screening for DR was provided to all subjects with DM in public primary care using digital fundus photography according to the English national screening programme. STDR was defined as preproliferative DR (R2), proliferative DR (R3) and/or maculopathy (M1). The presence of other eye diseases was noted. Visual impairment was classified as none (visual acuity in the better eye of 6/18 or better), mild (6/18 to >6/60) and severe (6/60 or worse). RESULTS: Of 174 532 subjects screened, most had never been screened before. The prevalence of DR was 39.0% (95% CI 38.8% to 39.2%) and STDR 9.8% (95% CI 9.7% to 9.9%). The most common DR status was R1 (35.7%), followed by M1 (8.6%), R2 (3.0%) and R3 (0.3%). The prevalence of mild and severe visual impairment was 4.2% and 1.3%, respectively. Subjects with STDR had a higher prevalence (9.8%) of visual impairment than those without (3.5%). CONCLUSIONS: DR was prevalent in this population and one in 10 had STDR. This suggests the need for systematic screening to ensure timely referral to an ophthalmologist for monitoring and/or treatment.

Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) complicated by retinopathy is associated with altered left ventricular (LV) structure and resting myocardial dysfunction unlike T2DM without retinopathy. The myocardial response to stress has not been compared in patients with and without diabetic retinopathy. The aim of this retrospective study was to determine the relationship between retinopathy and myocardial function in patients with T2DM at rest and during exercise echocardiography. METHODS: 134 patients with T2DM and no evidence of underlying coronary artery disease were recruited. All patients underwent retinal photography to screen for diabetic retinopathy, and resting and exercise echocardiography. Resting echocardiography was analyzed by conventional echocardiographic parameters and speckle tracking derived global longitudinal strain (GLS). Exercise echocardiography parameters included diastolic function reserve index (DFRI) and stress GLS. RESULTS: The mean age of participants was 60 years and 49% were male. Diabetic retinopathy was identified in 43 patients (32%). Resting echocardiography revealed that those with diabetic retinopathy had a higher prevalence of impaired diastolic function, higher E/E' ratio (LV filling pressures) and impaired resting GLS compared with those without. Exercise echocardiography revealed that those with diabetic retinopathy also had more impaired DFRI and stress GLS. Multivariable analysis showed that the presence of diabetic retinopathy was independently associated with high resting E/E', diastolic dysfunction grade, impaired resting GLS, low DFRI and impaired stress GLS. CONCLUSIONS: In conclusion, the presence of diabetic retinopathy was independently associated with impaired resting myocardial function (diastolic and systolic function) and myocardial function during stress (evaluated by DFRI and stress GLS).

Is it necessary to cover the macular hole with the inverted internal limiting membrane flap in macular hole surgery? A case report.

BACKGROUND: To report a case of late closure of idiopathic full-thickness macular hole (FTMH) after vitrectomy with the inverted internal limiting membrane (ILM) technique. CASE PRESENTATION: A 68-year-old lady with a stage IV FTMH underwent pars plana vitrectomy with 25 gauge plus transconjunctival system, ILM peeling and gas tamponade. The inverted ILM flap technique was adopted, except that no extra surgical manipulation was used to cover the macular hole with the ILM flap. Surgical outcome was monitored with serial optical coherence tomography (OCT). Complete closure of the FTMH with resolution of intraretinal cystic changes was confirmed on OCT at 16 months postoperatively. Visual acuity improved from a baseline level of 0.1 to 0.4. CONCLUSION: Idiopathic macular hole closure could be delayed to beyond 1 year following the inverted ILM flap technique, especially if the macular hole was not covered with the ILM flap. Not all macular holes that fail to close in the early postoperative period need to be re-operated and there may be no risk of further visual deterioration.

Bovine posterior limbus: an evaluation of an alternative source for corneal endothelial and trabecular meshwork stem/progenitor cells.

A growing body of evidence has revealed that stem-like cells in the posterior limbus of the eye between the corneal endothelium (CE) and trabecular meshwork (TM) may be able to rejuvenate these tissues in disease. However, these cells have not been clearly defined and we have named them PET cells (progenitor cells of the endothelium and trabeculum). A good and inexpensive animal model for PET cells is lacking, so we investigated bovine eyes as an effective large tissue source. We showed the presence of stem/progenitor cells in the bovine CE, transition zone, and TM in situ. Floating spheres cultured from the CE and TM showed similar stem cell marker expression patterns. Both the CE and TM spheres were bipotent and highly proliferative, but with limited secondary sphere-forming capability. They were highly prone to differentiate back into the cell type of their tissue of origin. It is speculated that the PET cells become more tissue-specific as they migrate away from their niche. Here, we showed that PET cells are present in the posterior limbus of bovine eyes and that they can be successfully cultured and expanded. PET cells represent an attractive target for developing new treatments to regenerate both the CE and TM, thereby reducing the requirement for donor tissue for corneal transplant and invasive treatments for glaucomatous patients.