-
Bioengineering (Basel, Switzerland) Jun 2024(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in...
(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in mice. In this study, the sensitivity of the mouse model to pharmaceutical therapy to reduce intraocular tension was assessed, the model's safety was confirmed using a cytotoxicity test, and the success rate of the mouse model of ocular hypertension was assessed by assessing alterations in IOP and neurons in the ganglion cell layer. (2) Methods: A mouse model of chronic ocular hypertension was produced in this study by employing photocrosslinkable sericin hydrogel injection and LED lamp irradiation. The eyes of 25 C57BL/6 male mice were subjected to 405 nm UV light from the front for 2 min after being injected with 5 μL of sericin hydrogel in the anterior chamber of the left eye. IOP in the mice was measured daily, and IOP rises greater than 5 mmHg were considered intraocular hypertension. When the IOP was lowered, the intervention was repeated once, but the interval between treatments was at least 2 weeks. The right eyes were not treated with anything as a normal control group. Mice eyeballs were stained with HE, Ni-type, and immunofluorescence to assess the model's efficacy. Two common drugs (tafluprost eye drops and timolol eye drops) were provided for one week after four weeks of stable IOP, and IOP changes were assessed to determine the drug sensitivity of the mouse model of chronic ocular hypertension. Furthermore, CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS) was utilized to investigate the safety of the ocular hypertension model by evaluating the deleterious effects of photocrosslinkable sericin hydrogel on cells. (3) Results: Before injection, the basal IOP was (9.42 ± 1.28) mmHg (1 kPa = 7.5 mmHg) in the experimental group and (9.08 ± 1.21) in the control group. After injection, cataract occurred in one eye, corneal edema in one eye, endophthalmitis in one eye, iris incarceration in one eye, and eyeball atrophy in one eye. Five mice with complications were excluded from the experiment, and twenty mice were left. Four weeks after injection, the IOP of the experimental group was maintained at (19.7 ± 4.52) mmHg, and that of the control group was maintained at (9.92 ± 1.55) mmHg, and the difference between the two groups was statistically significant ( < 0.05). Before the intervention, the IOP in the experimental group was (21.7 ± 3.31) mmHg in the high IOP control group, (20.33 ± 2.00) mmHg in the tafluprost eye drops group, and (20.67 ± 3.12) mmHg in the timolol maleate eye drops group. The IOP after the intervention was (23.2 ± 1.03) mmHg, (12.7 ± 2.11) mmHg, and (10.4 ± 1.43) mmHg, respectively. Before and after the intervention, there were no significant differences in the high-IOP control group ( > 0.05), there were statistically significant differences in the timolol eye drops group ( < 0.05), and there were statistically significant differences in the tafluprost eye drops group ( < 0.05). One week after drug withdrawal, there was no significant difference in IOP among the three groups ( > 0.05). In the high-IOP group, the protein (sericin hydrogel) showed a short strips or fragmented structure in the anterior chamber, accompanied by a large number of macrophages and a small number of plasma cells. The shape of the chamber angle was normal in the blank control group. The number of retinal ganglion cells decreased significantly 8 weeks after injection of sericin hydrogel into the anterior chamber, and the difference was statistically significant compared with the blank control group ( < 0.05). After the cells were treated with photocrosslinkable sericin hydrogel, there was no significant difference in the data of the CellTiter 96 assay kit of MTS compared with the blank control group ( > 0.05). (4) Conclusions: A mouse model of chronic intraocular hypertension can be established successfully by injecting sericin in the anterior chamber and irradiating with ultraviolet light. The model can simulate the structural and functional changes of glaucoma and can effectively reduce IOP after the action of most antihypertensive drugs, and it is highly sensitive to drugs. Sericin has no obvious toxic effect on cells and has high safety.
PubMed: 38927843
DOI: 10.3390/bioengineering11060607 -
Bioengineering (Basel, Switzerland) Jun 2024Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the... (Review)
Review
Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the tear film is lost. As the prevalence of both diseases increases with age, there is a high prevalence of DED among patients who are candidates for cataract surgery. In recent years, cataract surgery has evolved from vision restoration surgery to refractive surgery. To achieve good surgical outcomes, it is necessary to minimize postoperative refractive error in intraocular lens (IOL) power calculation, which requires accurate preoperative keratometry measurements. A stable tear film is important for the accuracy and reproducibility of keratometry measurements, and DED may have a deleterious effect. In this study, original articles that focused primarily on findings related to this topic were evaluated. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Although appropriate DED diagnoses were not presented in the articles evaluated in this review, it was confirmed that the clinical signs of DED, particularly the shortening of the tear film break-up time (TBUT), negatively impact IOL power calculations. Improvement in these clinical signs might mitigate the negative effects on these calculations.
PubMed: 38927833
DOI: 10.3390/bioengineering11060597 -
Genes Jun 2024Clouding of the transparent eye lens, or cataract(s), is a leading cause of visual impairment that requires surgical replacement with a synthetic intraocular lens to... (Review)
Review
Clouding of the transparent eye lens, or cataract(s), is a leading cause of visual impairment that requires surgical replacement with a synthetic intraocular lens to effectively restore clear vision. Most frequently, cataract is acquired with aging as a multifactorial or complex trait. Cataract may also be inherited as a classic Mendelian trait-often with an early or pediatric onset-with or without other ocular and/or systemic features. Since the early 1990s, over 85 genes and loci have been genetically associated with inherited and/or age-related forms of cataract. While many of these underlying genes-including those for lens crystallins, connexins, and transcription factors-recapitulate signature features of lens development and differentiation, an increasing cohort of unpredicted genes, including those involved in cell-signaling, membrane remodeling, and autophagy, has emerged-providing new insights regarding lens homeostasis and aging. This review provides a brief history of gene discovery for inherited and age-related forms of cataract compiled in the database and highlights potential gene-based therapeutic approaches to delay, reverse, or even prevent cataract formation that may help to reduce the increasing demand for cataract surgery.
Topics: Cataract; Humans; Lens, Crystalline; Animals; Crystallins; Aging
PubMed: 38927721
DOI: 10.3390/genes15060785 -
Genes May 2024The gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the... (Review)
Review
The gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the variants in the C-terminal DNA-binding domain associated with non-syndromic congenital cataracts and describe a patient with a novel, disease-causing de novo missense variant. Published reports of C-terminal variants and their associated congenital cataracts and ophthalmic findings were reviewed. The patient we present and his biological parents had genetic testing via a targeted gene panel followed by trio-based whole exome sequencing. A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in , NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified. We report the novel missense variant, c.922A>G (p.Lys308Glu), in the C-terminal DNA-binding domain of classified as likely pathogenic and associated with non-syndromic bilateral congenital cataracts.
Topics: Humans; Cataract; Proto-Oncogene Proteins c-maf; Mutation, Missense; Male; Child, Preschool; Protein Domains; Exome Sequencing
PubMed: 38927621
DOI: 10.3390/genes15060686 -
Journal of Cataract and Refractive... Jun 2024To develop and assess the utility of ophthalmic viscosurgical device (OVD) manufactured with fluorescein-conjugated hyaluronic acid (conjHA).
PURPOSE
To develop and assess the utility of ophthalmic viscosurgical device (OVD) manufactured with fluorescein-conjugated hyaluronic acid (conjHA).
SETTING
Department of Biomedical Engineering and the Wilmer Eye Institute, Johns Hopkins University and School of Medicine, Baltimore, MD, USA.
DESIGN
Laboratory study.
METHODS
ConjHA and unconjugated HA (unconjHA) at varied ratios were used to produce OVD (conjOVD) with varied fluorescence intensity. The conjHA:unconjHA ratio was optimized to maximize clarity under white light and fluorescence intensity under cobalt blue light (CBL), allowing for conditional visualization. The effect of conjugation on conjOVD viscosity was assessed via rotational rheometry. Intraocular lenses (IOLs) were immersed in conjOVD for 4 hours to assess staining of IOLs. A proof-of-concept study was performed in ex vivo porcine eyes. Following injection and visualization, the OVDs were removed from the eyes via irrigation/aspiration (I/A).
RESULTS
0.5 mg/mL of conjHA (degree of substitution=0.005) enabled robust fluorescence of conjOVD under CBL. Fluorescein-conjugation did not significantly affect conjOVD viscosity (P>0.05 for mean difference in viscosity at all shear rates tested). No staining of IOLs was appreciated. ConjOVD was visualized under CBL when injected ex vivo and maintained clarity of the anterior chamber under white light. Importantly, conjHA enabled delineation of retained OVD following I/A.
CONCLUSIONS
Use of OVD composed of fluorescein-conjugated HA is a feasible method to enable conditional visualization of OVD intraoperatively without nonspecific staining of ocular structures. Further development of this technology may enable accelerated OVD removal in ocular surgery or decreased OVD retention following surgery.
PubMed: 38926943
DOI: 10.1097/j.jcrs.0000000000001503 -
Scientific Reports Jun 2024This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We...
This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.
Topics: Humans; Male; Female; Smoking Cessation; Glaucoma; Middle Aged; Macular Degeneration; Retrospective Studies; Cataract; Taiwan; Aged; Adult; Smoking; Tobacco Use Cessation Devices; Incidence; Varenicline
PubMed: 38926484
DOI: 10.1038/s41598-024-65813-8 -
Ceska a Slovenska Oftalmologie :... 2024The authors present a case of a thirty-eight-year-old patient with Alport syndrome. The patient had several ocular symptoms of the disease and has been treated for...
The authors present a case of a thirty-eight-year-old patient with Alport syndrome. The patient had several ocular symptoms of the disease and has been treated for systemic problems in connection with Alport syndrome since he was fifteen years old. At that age the patient also underwent a kidney transplant in order to deal with renal insufficiency. To date, he still uses immunosuppressants and antihypertensives. Furthermore, the patient suffers from perceptive deafness. The patient visited our clinic in 2021 with a request to solve his high refractive error, in which the diopters were so high that it was not possible to place them in spectacles. The patient's best corrected visual acuity was 0.6 with -8.0sph/-4.0cyl/ax15 in the right eye and 0.7partim with -8.0sph/-4.0cyl/ax155 in the left eye. The autorefractometer values were -6.25sph/-6.75cyl/ax17 in the right eye and -6.75sph/-6.5cyl/ax155 in the left eye. During the eye examination we found a number of ocular manifestations that are typical of Alport syndrome. On the cornea there were opacities as a residue of corneal erosions, and at one of the following check-ups we also found a newly developed corneal erosion. Subsequently, we found an anterior lenticonus and incipient cataract. Upon performing OCT, a typical temporal macular atrophy was evident. Fundus examination in artificial mydriasis showed just a minimal manifestation of fleck retinopathy. Due to the clinical manifestation we decided to perform cataract surgery and implant a monofocal toric intraocular lens in both eyes. There were no complications during the operations, however the surgeon registered a non-standard structure of the lens capsule. The capsule was more fragile, and performing capsulorhexis was much more complicated. A week after the surgery, higher cylinder diopters were still present. A decrease of the higher diopters was noticeable one month after surgery. The time interval between the first operation and the second operation was one month. The patient was highly satisfied with result, and uncorrected visual acuity improved by over four lines. After surgery the patient needed low diopters for near as well as far distance. In the case of this patient, the ocular manifestations were detected and treated in adulthood. Nevertheless, early detection of ocular symptoms of Alport syndrome in young patients before renal failure could lead to timely start of the treatment and delay a possible renal transplant. In case of any suspicion of Alport syndrome it is advised to send the patient to a pediatrician, and at an older age to an internal medicine specialist, for further examination.
Topics: Humans; Nephritis, Hereditary; Male; Adult; Refractive Surgical Procedures; Visual Acuity
PubMed: 38925900
DOI: 10.31348/2024/28 -
Aging Jun 2024Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them...
Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.
PubMed: 38925660
DOI: 10.18632/aging.205963 -
Protein Science : a Publication of the... Jul 2024Conserved tryptophan residues are critical for the structure and the stability of β/γ-crystallin in the lenses of vertebrates. During aging, in which the lenses are...
Conserved tryptophan residues are critical for the structure and the stability of β/γ-crystallin in the lenses of vertebrates. During aging, in which the lenses are continuously exposed to ultraviolet irradiation and other environmental stresses, oxidation of tryptophan residues in β/γ-crystallin is triggered and impacts the lens proteins to varying degrees. Kynurenine derivatives, formed by oxidation of tryptophan, accumulate, resulting in destabilization and insolubilization of β/γ-crystallin, which correlates with age-related cataract formation. To understand the contribution of tryptophan modification on the structure and stability of human βB2-crystallin, five tryptophan residues were mutated to phenylalanine considering its similarity in structure and hydrophilicity to kynurenine. Among all mutants, W59F and W151F altered the stability and homo-oligomerization of βB2-crystallin-W59F promoted tetramerization whereas W151F blocked oligomerization. Most W59F dimers transformed into tetramer in a month, and the separated dimer and tetramer of W59F demonstrated different structures and hydrophobicity, implying that the biochemical properties of βB2-crystallin vary over time. By using SAXS, we found that the dimer of βB2-crystallin in solution resembled the lattice βB1-crystallin dimer (face-en-face), whereas the tetramer of βB2-crystallin in solution resembled its lattice tetramer (domain-swapped). Our results suggest that homo-oligomerization of βB2-crystallin includes potential inter-subunit reactions, such as dissociation, unfolding, and re-formation of the dimers into a tetramer in solution. The W>F mutants are useful in studying different folding states of βB2-crystallin in lens.
Topics: Humans; Protein Folding; Tryptophan; beta-Crystallin B Chain; Mutation; Protein Multimerization; Protein Stability; Hydrophobic and Hydrophilic Interactions; Amino Acid Substitution
PubMed: 38924206
DOI: 10.1002/pro.5092 -
International Ophthalmology Jun 2024To examine the rate of ciliary body detachment in patients with choroidal detachment following glaucoma surgery and its effect on the clinical course, management, and... (Observational Study)
Observational Study
PURPOSE
To examine the rate of ciliary body detachment in patients with choroidal detachment following glaucoma surgery and its effect on the clinical course, management, and prognosis.
METHODS
A prospective observational case-series study. Patients with choroidal detachment following glaucoma surgery in 2018-2019 were included. All underwent complete ophthalmological examination and ultrasound biomicroscopy for evaluation of the presence and extent of ciliary body detachment. Follow-up examinations including ultrasound biomicroscopy scans were performed at 1 week, 1 month, 3 months, and 6 months.
RESULTS
Eight patients (8 eyes) were enrolled, 4 male and 4 female, of mean age 72 years (range 60-83). Five patients underwent trabeculectomy with mitomycin C (0.02%), which was combined with phacoemulsification cataract extraction in one; two underwent Ahmed glaucoma valve implantations, and one underwent ab-interno Xen45 gel stent implantation with mitomycin C (0.02%). The mean intraocular pressure was 26.0 ± 7.65 mmHg preoperatively, dropping to 6.9 ± 2.64 mmHg on first postoperative day one. Mean time from surgery to diagnosis of choroidal detachment was 11.6 ± 5.73 days. Ciliary body detachment was identified by ultrasound biomicroscopy in all patients, ranging between one and four quadrants. All patients were treated with topical steroids and cycloplegics; three (37.5%) received oral steroids. No surgical intervention for the choroidal or ciliary body detachments was indicated.
CONCLUSIONS
In this real-world prospective study, concurrent ciliary body detachment was identified in all patients who presented with choroidal detachment following glaucoma surgery. This observation may deepen our understanding of the mechanism underlying the hypotony that is often seen after glaucoma surgery.
Topics: Humans; Male; Female; Ciliary Body; Aged; Prospective Studies; Middle Aged; Aged, 80 and over; Intraocular Pressure; Choroidal Effusions; Glaucoma; Postoperative Complications; Microscopy, Acoustic; Follow-Up Studies; Trabeculectomy; Glaucoma Drainage Implants; Visual Acuity; Uveal Diseases; Tomography, Optical Coherence
PubMed: 38922523
DOI: 10.1007/s10792-024-03219-1