Müller cells are glial cells of the retina, whose major processes cross the internal and external limiting membranes of the retina, maintaining the function and metabolism of retinal photoreceptors and neurons. Their structure and function are closely related to the development of macular hole (MH). Müller cells are involved in the formation and recovery of MH from the aspect of traction and protein, and their morphology and biological function also influence the regression of MH. The current treatment modality for MH is vitrectomy combined with internal limiting membrane (ILM) peeling, in which Müller cells play a dual role after ILM peeling in different stages of MH. And its potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons making it a current research hot topic, which can be a reference and inspiration for clinical treatment.
ObjectiveTo observe the effects of overexpression of S100A4 protein on retinal capillary cells and retinal ganglion cells (RGC) after retinal ischemia-reperfusion injury (RIRI). MethodsOne hundred healthy adult male C57BL/6 mice were randomly divided into normal control group (group C), RIRI group, adeno-associated virus (AAV2)-S100A4 green fluorescent protein (GFP) intravitreal injection group (group S), RIRI+AAV2-GFP intravitreal injection group (group GIR), and RIRI+AAV2-S100A4-GFP intravitreal injection group (group SIR), with 20 mice in each group. The RIRI model was established using the high intraocular pressure anterior chamber method in the RIRI, GIR and SIR groups of mice. Eyes were enucleated 3 days after modelling by over anaesthesia. The number of retinal capillary endothelial cells and pericytes in the retinal capillaries of mice in each group was observed by retinal trypsinised sections and hematoxylin-eosin and periodic acid-Schiff staining; immunofluorescence staining was used to observe endothelial cell, pericyte coverage and RGC survival; The relative expression of Toll-like receptor 4 (TLR4), p38 MAPK and nuclear factor erythroid 2-related factor 2 (NRF2) in retinal tissues was measured by Western blot. One-way analysis of variance was used to compare data between groups. ResultsThree days after modeling, the endothelial cell to pericyte ratio in group C was compared with group S and SIR, and the difference was not statistically significant (F=106.30, P＞0.05); the SIR group was compared with group RIRI and GIR, and the difference was statistically significant (F=106.30, P＜0.000 1). Comparison of endothelial cell coverage in each group, the difference was not statistically significant (F=3.44, P＞0.05); compared with the pericyte coverage in group C, the RIRI group and the GIR group were significantly lower, and the difference was statistically significant (F=62.69, P＜0.001). Compared with the RGC survival rate in group C, it was significantly lower in RIRI and GIR groups, and the difference was statistically significant (F=171.60, P＜0.000 1); compared with RIRI and GIR groups, the RGC survival rate in SIR group was significantly higher, and the difference was statistically significant (F=171.60, P＜0.000 1). The relative expression levels of TLR4, p38 and NRF2 proteins were statistically significant among all groups (F=42.65, 20.78, 11.55; P＜0.05). ConclusionsPericytes are more sensitive to ischemia than endothelial cells after retinal RIRI in mice, and early vascular cell loss is dominated by pericytes rather than endothelial cells. The overexpression of S100A4 protein protects against loss of pericytes and RGC after RIRI by inhibiting the TLR4/p38/NRF2 signaling pathway.
ObjectiveTo compare the efficacy of internal limiting membrane (ILM) flip coverage with ILM multilayer tamponade in the treatment of highly myopic macular hole-associated retinal detachment (MHRD). MethodsA retrospective clinical study. From November 2019 to June 2022, 53 cases and 53 eyes of MHRD patients who were examined and diagnosed at the Eye Centre of Renmin Hospital of Wuhan University were included in the study. Among them, 21 cases and 21 eyes were male and 32 cases and 32 eyes were female. The age was (55.28±11.40) years. The patients were categorized into two groups: the ILM coverage group (from November 2019 to September 2020) and the ILM multilayer tamponade group (from October 2020 to June 2022) based on their surgical procedures. The ILM coverage group comprised of 11 cases involving 11 eyes, while the ILM multilayer tamponade group comprised of 42 cases involving 42 eyes. Best-corrected visual acuity (BCVA) and optical coherence tomography were conducted. BCVA was measured using standardized international visual acuity charts and transformed to logarithmic minimum angle of resolution (logMAR) visual acuity for statistical analysis. The affected eyes were all treated with standard transciliary flattening three-channel 23-gauge vitrectomy. The inverted ILM flap technique was combined with flap coverage in the inverted group, while the ILM multilayer tamponade group used circular ILM stripping to preserve the ILM in the macular area and ILM flap around the macular hole with multilayer ILM tamponade. Postoperative follow-up was carried out for a minimum of 6 months. Relevant examinations were conducted during the follow-up using the same equipment and methods as those used before surgery. The BCVA, as well as the closure of macular hole, resurfacing of the retina, and development of macular hyperplasia, were observed. ResultsIn the ILM-covered group, the macular hole was closed in 7 out of 11 eyes after 1 week of surgery. At 1 month after surgery, the macular hole was closed in all treated eyes. At 6 months after surgery, the macular hole was closed in 9 eyes, while 2 eyes were reopened. In 42 eyes from the ILM-multilayer tamponade group, the macular hole closed after surgery in 41 eyes. At 6 months postoperatively, best corrected visual acuity (BCVA) of eyes in ILM-covered and ILM-multilayer tamponade groups was 0.91±0.29 and 1.05±0.39, respectively, with no statistically significant difference between the two groups (t=1.140, P=0.260). The BCVA of the eyes in both groups showed a significant improvement compared to the preoperative period with a statistically significant difference (t=8.490, 13.840; P＜0.000 1); 6 months after surgery, 10 out of 11 eyes in the ILM coverage group had a restored retina with no detectable macular hyperplasia; 42 eyes in the ILM multilayer tamponade group had a restored retina, but 19 of these eyes had detectable macular hyperplasia. ConclusionsEither ILM flap coverage or ILM multilayer tamponade contributes to high myopic MHRD closure and improved visual acuity. Compared to ILM flap coverage, ILM multilayer tamponade results in higher and earlier rates of macular hole closure and lower rates of macular hole reopening. However, ILM multilayer tamponade may lead to a higher proportion of macular hyperplasia formation without affecting visual acuity recovery at 6 months after surgery.