Genetic information is stored in the bases of double-stranded DNA. However, the integrity of DNA molecules is constantly threatened by various mutagenic agents, including pollutants, ultraviolet light (UV), and medications. To counteract these environmental damages, cells have established multiple mechanisms, such as producing molecules to identify and eliminate damaged DNA, as well as reconstruct the original DNA structures. Failure or insufficiency of these mechanisms can cause genetic instability. However, the role of genome stability in eye diseases is still under-researched, despite extensive study in cancer biology.
Main text
As the eye is directly exposed to the external environment, the genetic materials of ocular cells are constantly under threat. Some of the proteins essential for DNA damage repair, such as pRb, p53, and RAD21, are also key during the ocular disease development. In this review, we discuss five ocular diseases that are associated with genomic instability. Retinoblastoma and pterygium are linked to abnormal cell cycles. Fuchs’ corneal endothelial dystrophy and age-related macular degeneration are related to the accumulation of DNA damage caused by oxidative damage and UV. The mutation of the subunit of the cohesin complex during eye development is linked to sclerocornea.
Conclusions
Failure of DNA damage detection or repair leads to increased genomic instability. Deciphering the role of genomic instability in ocular diseases can lead to the development of new treatments and strategies, such as protecting vulnerable cells from risk factors or intensifying damage to unwanted cells.
Retinal diseases characterized with irreversible loss of retinal nerve cells, such as optic atrophy and retinal degeneration, are the main causes of blindness. Current treatments for these diseases are very limited. An emerging treatment strategy is to induce the reprogramming of Müller glial cells to generate new retinal nerve cells, which could potentially restore vision.
Main text
Müller glial cells are the predominant glial cells in retinae and play multiple roles to maintain retinal homeostasis. In lower vertebrates, such as in zebrafish, Müller glial cells can undergo cell reprogramming to regenerate new retinal neurons in response to various damage factors, while in mammals, this ability is limited. Interestingly, with proper treatments, Müller glial cells can display the potential for regeneration of retinal neurons in mammalian retinae. Recent studies have revealed that dozens of genetic and epigenetic regulators play a vital role in inducing the reprogramming of Müller glial cells in vivo. This review summarizes these critical regulators for Müller glial cell reprogramming and highlights their differences between zebrafish and mammals.
Conclusions
A number of factors have been identified as the important regulators in Müller glial cell reprogramming. The early response of Müller glial cells upon acute retinal injury, such as the regulation in the exit from quiescent state, the initiation of reactive gliosis, and the re-entry of cell cycle of Müller glial cells, displays significant difference between mouse and zebrafish, which may be mediated by the diverse regulation of Notch and TGFβ (transforming growth factor-β) isoforms and different chromatin accessibility.
To establish a comprehensive treatment strategy and evaluate the efficacy of combination of anti-vascular endothelial growth factor (VEGF) injection, pars plana vitrectomy (PPV), endoscopic pan-retinal photocoagulation (PRP), and endoscopic cyclophotocoagulation (ECP) surgery for neovascular glaucoma (NVG) patients.
Methods
This retrospective study included 30 patients (30 eyes) who were suffering from NVG and treated with PPV & PRP & ECP (ECP group, 16 eyes), or Ahmed glaucoma valve implantation (Ahmed group, 14 eyes). The intraocular pressure (IOP), number of postoperative anti-glaucoma medications, best-corrected visual acuity (BCVA), successful rate of surgery, and postoperative complications were recorded and statistically analyzed at the time points of preoperative, 1-day, 1-month, 3-months, 6-months, and 12-months after operation.
Results
An obvious reduction in IOP and number of postoperative anti-glaucoma medications were observed in both the ECP group and Ahmed group after operation (P < 0.05), and the ECP group showed a significantly lower IOP compared to the Ahmed group at the 6-months (P = 0.014) and 12-months (P = 0.047) postoperative time points, while there was no significant difference of medication number between the two groups except for 1-day after surgery. The BCVA showed no marked difference between the two groups preoperatively and postoperatively (P > 0.05), while it was significantly improved in ECP group at 3-months (P = 0.001), 6-months (P = 0.004), and 12-months (P = 0.010) time points comparing with preoperative BCVA. The surgical success rates in ECP group were also slightly higher than Ahmed group. And the complications after operation showed no marked differences.
Conclusions
The comprehensive treatment of PPV, endoscopic PRP, and ECP surgery for NVG patients after anti-VEGF injection can control IOP effectively and be friendly to patients’ BCVA without obvious serious complications throughout a 12-months follow-up period.
To quantitatively measure and compare the vascular morphology in healthy eyes and eyes with primary open-angle glaucoma (POAG) using optical coherence tomography angiography (OCTA) scans.
Methods
This is a retrospective and cross-sectional study which include healthy individuals and individuals with POAG that underwent OCTA imaging at an academic center's glaucoma clinic. We analyzed OCTA scans of the macula and optic nerve head (ONH) of one eye from each subject to quantitatively measure vessel density (VD), vessel length density (VLD), and branchpoint density (BPD). We compared these 3 parameters between the healthy and POAG groups and used logistic regression classification models to determine their diagnostic value in differentiating healthy and glaucomatous eyes.
Results
We included 49 healthy subjects and 49 subjects with POAG. After age-adjusted analysis, the parameters of VD, VLD, and BPD were significantly reduced in eyes with POAG (P < 0.001) in all scan layers and most significantly around the ONH. The parameter with the best performances were radial peripapillary capillary (RPC) VD [AUC (areas under the curve): 0.939 (0.891, 0.987)] which had statistically higher performances (P < 0.05) than parameters in the superficial or deep layers. All 3 parameters in the RPC layer had statistically similar performances.
Conclusions
We found that VD, VLD, and BPD were reduced in glaucomatous eyes. The morphologic parameters of VLD and BPD had similar performances to the traditional parameter of VD in RPC layers. Our results suggest that vascular morphology parameters may provide additional value in the diagnosis and evaluation of glaucoma.
To report the clinical consequences and laboratory characteristics of late postoperative opacification of a hydrophilic acrylic intraocular lens (US-860UV IOL) as well as the prognosis of IOL replacement.
Methods
Forty medical records (42 eyes) of patients with US-860UV IOL opacification reporting decreased or lost vision who underwent IOL explantation between 2017 and 2019 were reviewed. Explanted IOLs were analyzed by slit-lamp examination, confocal microscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) at the Shandong Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, and Qingdao University of Science and Technology, Qingdao, China.
Results
The mean age of the 40 patients was 74.83 ± 7.57 (63–92) years. The mean interval between cataract surgery and diagnosis of opacification was 32.38 ± 8.76 (17–48) months. Systemic diseases were found without statistical correlations, the most frequent being arterial hypertension, coronary heart disease, and diabetes mellitus. Visual acuity improved from 1.42 ± 1.03 to 0.31 ± 0.16 (logMAR) after IOL replacement. SEM, EDS and alizarin red staining showed uniformly distributed, diffuse, milk-white opacification, with calcium and phosphorus deposits on the optic and haptic surfaces that could be dissolved in 1% HCl.
Conclusions
Calcium and phosphorus deposition was the main cause of hydrophilic acrylic US-860UV IOL opacification. IOL replacement can safely and effectively improve the visual acuity of patients.
To observe the clinical and imaging characteristics of radiation-induced optic neuropathy (RION).
Methods
We retrospectively reviewed the clinical data of 43 patients (69 eyes) who were diagnosed with RION at the Chinese PLA General Hospital from 2010 to 2021.
Results
The latency from radiotherapy to onset of visual loss ranged from 1 to 132 (36.33 ± 30.48) months. Optic disc pallor and optic disc edema were found in 27.0% (10/37) and 8.1% (3/37) of the eyes, respectively, within 2 months. After treatment, the best corrected visual acuity (BCVA) was restored in 24.6% (17/69) of the eyes and the final BCVA improved in 13.0% (9/69) of the eyes. An 82.5% (33/40) of the eyes with magnetic resonance imaging (MRI) showed enhancement of the affected optic nerve, mostly (69.7%) in the intracranial segment, and 36.4% (12/33) of the eyes with expansion and T2-high signals also showed enhancement of the affected optic nerve. The superior retinal nerve fiber layer (RNFL) and the outer circle superior quadrant (OS) of the inner limiting membrane to retinal pigment epithelium (ILM-RPE) layer thinned significantly during the first month. The center of the ILM-RPE layer thickened significantly during the first two months and the inner circle temporal quadrant (IT) of the ILM-RPE layer thickened significantly from the third to sixth month. The RNFL thinned significantly after 6 months except for the temporal quadrant, and the average inner circle superior quadrant (IS) and outer circle of the ILM-RPE layer thinned significantly after 6 months. There was no significant difference between hyperbaric oxygen therapy (HBOT) and high-dose intravenous methylprednisolone (IVMP) therapy in improving BCVA recovery or final BCVA (P > 0.05).
Conclusions
The structural damage of the RNFL and ILM-RPE layer occurred during the first month, the RNFL showed progressive thinning during the follow-up period, while the ILM-RPE layer showed thinning during the first month, thickening from the third to sixth month, and thinning after 6 months. There was a discrete region of enhancement of the optic nerve, often with expansion and high-T2 signals on MRI. HBOT and high-dose IVMP therapy were hardly effective for treating RION in the non-acute stage.
To evaluate near, intermediate, distance visual acuity and stereopsis after bilateral implantation of Toric intraocular lenses (IOLs) in high myopic patients with astigmatism.
Methods
Bilateral Toric or non-Toric IOL implantation (n = 40 eyes each) was performed on high myopic cataract eyes with astigmatism. Best-corrected distance visual acuity (BCDVA), uncorrected intermediate visual acuity (UCIVA), uncorrected near visual acuity (UCNVA), residual refractive astigmatism (RRA), and near, intermediate, and distance stereoacuity were measured postoperatively at 7 days, 1 month, and 3 months.
Results
The three-month postoperative BCDVA, UCIVA, and UCNVA of the Toric group were 0.08 ± 0.07, 0.30 ± 0.11, and 0.23 ± 0.14 LogMAR. All improved over the preoperative assessments (P < 0.05). The RRA, UCIVA, and UCNVA were significantly better in the Toric group than the non-Toric group at all follow-up examinations (all P < 0.05). At 3 months, the median near and intermediate stereoacuity of the Toric group were 100 (range 40 – 400) and 120 (range 50 – 400) arcsec, which were better than the non-Toric group (both P < 0.05). Fine near stereopsis ≥100 arcsec was present in 65% of the Toric patients, and 50% had good intermediate stereopsis of ≥100 arcsec. However among non-Toric patients, only 15% and 5% achieved fine near and intermediate stereopsis. The postoperative BCDVA and best-corrected distance stereoacuity were similar in the two groups (P > 0.05).
Conclusions
In bilateral high myopic cataract patients with astigmatism, Toric IOLs not only improved UCIVA, UCNVA, and RRA, but also enhanced near and intermediate stereopsis acuity.