Impact of Arterial Hypertension on the Eye: A Review of the Pathogenesis, Diagnostic Methods, and Treatment of Hypertensive Retinopathy.

The number of patients with arterial hypertension is continually increasing. Hypertension can cause organ complications, called hypertension-mediated organ damage (HMOD). One example is hypertensive retinopathy, in which high blood pressure (BP) damages both the retinal microcirculation and the retinal nerve fiber layer (RNFL). This can result in progressive and painless vision deterioration in some groups of patients. Unlike anywhere else in the human body, the microvasculature of the retina can be observed in vivo, and the progression of changes can be closely monitored. The harmful effect of increased BP on the eye is not only limited to hypertensive retinopathy, but can also lead to an exacerbation of diabetic retinopathy (DR) and to an increase in intraocular pressure (IOP), and it can also trigger the formation of thromboembolic lesions. This review presents an update on the pathogenesis of hypertensive retinopathy and the use of adaptive optics (AO) combined with optical coherence tomography (OCT) to evaluate the retinal microvasculature. The latest progress and directions of research in the field of hypertensive retinopathy are also discussed.

Immunological and molecular basics of the primary open angle glaucoma pathomechanism.

Glaucoma is a degenerative process of the optic nerve. Increased intraocular pressure is believed to be the main factor leading to the glaucomatous damage. The in vitro and in vivo animal glaucoma research models provide insight into the molecular changes in the retina in response to the injury factor. The damage is a complex process incorporating molecular and immunological changes. Such changes involve NF kB activity and complement activation. The processes affect the human antigen, JNK, MAPK, p53, MT2 and DBA/2J molecular pathways, activate the autophagy processes and compromise neuroprotective mechanisms. Activation and inhibition of immunological responses contribute to cell injury. The immunological mechanisms of glaucomatous degeneration include glial response, the complement, tumor necrosis factor α (TNF-α) pathways and toll-like receptors athways. Oxidative stress and excitotoxicity are factors contributing to cell death in glaucoma. The authors present an up-to-date review of the mechanisms involved and update on research focusing on a possible innovative glaucoma treatment.

Utilization of the Reinstein ICL Sizing Formula With Hand-held Ultrasound Biomicroscopy Measurements.

PURPOSE: To evaluate the accuracy of the Reinstein formula with hand-held ultrasound biomicroscopy (UBM) measurements for sizing of the Implantable Collamer Lens (ICL). METHODS: A total of 107 myopic eyes of 57 patients implanted with the ICL were included in the study. The size of the ICL was selected based on the manufacturer's recommendations. Agreement between the vault predicted by the Reinstein formula and the vault measured postoperatively was analyzed with Bland-Altman plots. RESULTS: A total of 95% and 81% of patients had a postoperative vault ranging from 150 to 1,000 and 250 to 750 µm, respectively. The mean vault predicted by the Reinstein formula and the postoperative vault in the current study were 580 ± 181 and 547 ± 200 µm, respectively. The size recommendations of the Reinstein formula and the formula provided by the manufacturer, the Kojima formula, and the Dougherty formula overlapped in 50%, 57%, and 49% of eyes, respectively. CONCLUSIONS: The results show that the Reinstein formula combined with a hand-held UBM provides reliable sizing predictions of the ICL. However, considering that robotic UBM measurements have demonstrated a narrower range of deviation in predicting vault depth in previous studies, a direct comparison study between robotic UBM and hand-held UBM measurements is necessary to fully assess the limitations of combining hand-held UBM with the Reinstein formula. [J Refract Surg. 2024;40(3):e142-e147.].

An association of transferrin gene polymorphism and serum transferrin levels with age-related macular degeneration.

Age-related macular degeneration (AMD) is a degenerative disease of the eye, triggered by the damage of the macular cells. In the Western world it is the most frequent cause of blindness in the elderly. Oxidative stress is proved to play a key role in AMD pathogenesis and since iron accumulation has been found in AMD maculas, it may accelerate the oxidative processes in this tissue. In the present work we investigated the association between four polymorphisms of the transferrin gene (rs8177178; rs8177179; rs4481157; rs1130459) and AMD in dependence on the transferrin protein and iron serum levels. We employed PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) for genotype determination, ELISA assay for serum transferrin evaluation and colorimetric assay for measurement of iron concentration in the serum. We found that advanced age and AMD family history may be independent risk factors for AMD (1.02, p < 0.05 and 8.88, p < 0.001, respectively). At the rs4481157 site The GG genotype of the rs4481157 polymorphism decreased the risk of dry AMD (OR 0.50; p < 0.05), while the GA increased this risk (OR 1.07; p < 0.05). Moreover, the GA genotype of this polymorphism decreased the risk of progression to the wet form (OR 0.63; p < 0.05). The analysis of the gene-environment interactions showed that the rs4481157 polymorphism modulates the AMD risk among obese (BMI above 30) individuals. In the former smokers group we observed a moderate association between rs4481157 polymorphism and AMD risk while this association in current smokers was stronger. We found also that the serum level of transferrin was higher in the AMD group (p < 0.001) than in the control, but the total serum iron levels did not differ between both groups. We found that the serum transferrin was associated with the rs8177178 (p < 0.001) and rs4481157 (p < 0.01) polymorphisms, and the common variant (GG) of both sites was related to a lower level of transferrin. Presented data may contribute to the involvement of iron homeostasis in AMD risk.

Progression of Rare Inherited Retinal Dystrophies May Be Monitored by Adaptive Optics Imaging.

Inherited retinal dystrophies (IRDs) are bilateral genetic conditions of the retina, leading to irreversible vision loss. This study included 55 eyes afflicted with IRDs affecting the macula. The diseases examined encompassed Stargardt disease (STGD), cone dystrophy (CD), and cone-rod dystrophy (CRD) using adaptive optics (Rtx1™; Imagine Eyes, Orsay, France). Adaptive optics facilitate high-quality visualisation of retinal microstructures, including cones. Cone parameters, such as cone density (DM), cone spacing (SM), and regularity (REG), were analysed. The best corrected visual acuity (BCVA) was assessed as well. Examinations were performed twice over a 6-year observation period. A significant change was observed in DM (1282.73/mm2 vs. 10,073.42/mm2, p< 0.001) and SM (9.83 µm vs. 12.16 µm, p< 0.001) during the follow-up. BCVA deterioration was also significant (0.16 vs. 0.12, p = 0.001), albeit uncorrelated with the change in cone parameters. No significant difference in REG was detected between the initial examination and the follow-up (p = 0.089).

Characteristics of Rare Inherited Retinal Dystrophies in Adaptive Optics-A Study on 53 Eyes.

Inherited retinal dystrophies (IRDs) are genetic disorders that lead to the bilateral degeneration of the retina, causing irreversible vision loss. These conditions often manifest during the first and second decades of life, and their primary symptoms can be non-specific. Diagnostic processes encompass assessments of best-corrected visual acuity, fundoscopy, optical coherence tomography, fundus autofluorescence, fluorescein angiography, electrophysiological tests, and genetic testing. This study focuses on the application of adaptive optics (AO), a non-invasive retinal examination, for the assessment of patients with IRDs. AO facilitates the high-quality, detailed observation of retinal photoreceptor structures (cones and rods) and enables the quantitative analysis of parameters such as cone density (DM), cone spacing (SM), cone regularity (REG), and Voronoi analysis (N%6). AO examinations were conducted on eyes diagnosed with Stargardt disease (STGD, N=36), cone dystrophy (CD, N=9), and cone-rod dystrophy (CRD, N=8), and on healthy eyes (N=14). There were significant differences in the DM, SM, REG, and N%6 parameters between the healthy and IRD-affected eyes (p<0.001 for DM, SM, and REG; p=0.008 for N%6). The mean DM in the CD, CRD, and STGD groups was 8900.39/mm2, 9296.32/mm2, and 16,209.66/mm2, respectively, with a significant inter-group difference (p=0.006). The mean SM in the CD, CRD, and STGD groups was 12.37 µm, 14.82 µm, and 9.65 µm, respectively, with a significant difference observed between groups (p=0.002). However, no significant difference was found in REG and N%6 among the CD, CRD, and STGD groups. Significant differences were found in SM and DM between CD and STGD (p=0.014 for SM; p=0.003 for DM) and between CRD and STGD (p=0.027 for SM; p=0.003 for DM). Our findings suggest that AO holds significant potential as an impactful diagnostic tool for IRDs.

Spherical aberrations and their role in modern ophthalmology.

Spherical aberration is an imperfection of the optical system of the human eye. The role of spherical aberration of the human eye in the quality of vision and pseudoaccommodation is reviewed. Spherical aberration is an imperfection of the optical system of the human eye. In most cases, due to well-developed neuroadaptation, it is insignificant for the perception of the image. Nevertheless, its role in modern ophthalmology is far from straightforward. On the one hand, there are clinical scenarios in which an excess of spherical aberration degrades the retinal image and leads to a high dissatisfaction rate among patients.©Recently, there is a growing interest in the modulation of spherical aberration in the clinical setting. Modern intraocular lenses as well as laser refractive procedures are aimed at interfering with spherical aberrations of the optical system in order to increase range of pseudoaccommodation. Here, we review the role of spherical aberration of the human eye in the quality of vision and pseudoaccommodation.

Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration.

Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber-Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found (OR 3.40, 4.15, and 2.75). On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form (OR 0.23, 0.21, 0.26). Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD.

An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration.

Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber-Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the -42 + 1444 position in the HMOX2 gene (the -42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the -42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the -42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the -42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the -42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD.

Clinical Performance of Extended Depth of Focus (EDOF) Intraocular Lenses - A Retrospective Comparative Study of Mini Well Ready and Symfony.

Purpose: Extended depth of focus intraocular (EDOF) IOLs form a bridge between single- and multifocal IOL design. This study aimed to compare clinical outcomes obtained after implanting two different optical designs of EDOF IOLs: the Mini Well Ready (SIFI Medtech, Catania, Italy) and Tecnis Symfony (Abbott Laboratories, Illinois, USA). Methods: The retrospective observational study included 61 patients (122 eyes) who underwent bilateral implantation of the Mini Well Ready IOL (32 patients) or the Tecnis Symfony IOL (29 patients). The following preoperative and postoperative parameters were evaluated: spherical equivalent, anterior astigmatism, pupil size, monocular and binocular uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), monocular and binocular uncorrected intermediate visual acuity (UIVA) and distance-corrected intermediate visual acuity (DCIVA), monocular and binocular uncorrected near visual acuity (UNVA) and distance-corrected near visual acuity (DCNVA). In the 6 months postoperative period, defocus curve, contrast sensitivity, photopic phenomena, and posterior capsule opacification were assessed. Results: The patients receiving the Tecnis Symfony had slightly better monocular and binocular UDVA and CDVA than with the Mini Well Ready IOL, the differences were not statistically significant. Whereas the UIVA, DCIVA, UNVA, DCNVA, UNVA and DCNVA values were higher in the Mini Well Ready group, the differences were not significant. There were no significant between-group differences regarding the defocus curve for the vast majority of tested vergences. Dysphotopsias postoperatively were assessed at 6 months. Conclusion: Patients receiving both the Mini Well Ready and Symfony IOLs had excellent visual acuity outcomes and spectacle independence.

Effect of COVID-19 Lockdowns on Eye Emergency Department, Increasing Prevalence of Uveitis and Optic Neuritis in the COVID-19 Era.

Background: The COVID-19 pandemic led to the reorganization of the health care system. A decline in health- and life-saving procedures has been reported in various medical specialties. However, data on ophthalmic emergencies during lockdowns is limited. Methods: We conducted a retrospective, observational, case-control study of 2351 patients registered at the ophthalmic emergency department of a tertiary hospital in Poland during three national COVID-19 lockdowns (March/April 2020, November 2020, and March/April 2021) and corresponding months in 2019. Results: The total number of visits declined from a mean of 720/month in the non-COVID era to 304/month during COVID-19 lockdowns (p < 0.001). Ocular trauma incidence dropped significantly from 2019 (non-COVID months) to 2020/2021 (COVID group mean 201 vs. 97 patients monthly, respectively, p = 0.03). Of note, the percentage of foreign bodies removal was significantly higher during lockdowns than corresponding time in the non-COVID era. A downward trend for vitreous detachment and macular disorders cases was observed between COVID and non-COVID time. Uveitis and optic neuritis patients were seen more often during lockdowns (p < 0.001 and p = 0.0013, respectively). In contrast, the frequency of conjunctivitis and keratitis, potentially COVID-related problems, decreased significantly in COVID-19 time (mean 138 vs. 23 per month in non-COVID vs. COVID lockdowns, respectively, p < 0.001). Conclusions: The overall number of eye emergency visits declined during COVID-19 lockdowns. Conjunctivitis and keratitis rates dropped during the lockdowns. Interestingly, the frequency of immune-mediated ocular conditions (uveitis, optic neuritis) increased significantly which might be triggered by SARS-CoV2 infection.

Protective effect of chitosan oligosaccharide lactate against DNA double-strand breaks induced by a model methacrylate dental adhesive.

BACKGROUND: Monomers of methacrylates used in restorative dentistry have been recently reported to induce DNA double-strand breaks (DSBs) in human gingival fibroblasts (HGFs) in vitro. Because such monomers may penetrate the pulp and oral cavity due to the incompleteness of polymerization and polymer degradation, they may induce a similar effect in vivo. DSBs are the most serious type of DNA damage and if misrepaired or not repaired may lead to mutation, cancer transformation and cell death. Therefore, the protection against DSBs induced by methacrylate monomers released from dental restorations is imperative. MATERIAL/METHODS: We examined the protective action of chitosan oligosaccharide lactate (ChOL) against cytotoxic and genotoxic effects induced by monomers of the model adhesive consisting of 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) and 45% 2-hydroxyethyl methacrylate (HEMA). We evaluated the extent of DSBs by the neutral comet assay and the phosphorylation of the H2AX histone test. RESULTS: ChOL increased the viability of HGFs exposed to Bis-GMA/HEMA as assessed by flow cytometry. ChOL decreased the extent of DSBs induced by Bis-GMA/HEMA as evaluated by neutral comet assay and phosphorylation of the H2AX histone. ChOL did not change mechanical properties of the model adhesive, as checked by the shear bond test. Scanning electron microscopy revealed a better sealing of the dentinal microtubules in the presence of ChOL, which may protect pulp cells against the harmful action of the monomers. CONCLUSIONS: ChOL can be considered as an additive to methacrylate-based dental materials to prevent DSBs induction, but further studies are needed on its formulation with the methacrylates.

Lack of association between the c.544G>A polymorphism of the heme oxygenase-2 gene and age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a primary cause of blindness among the elderly in developed countries. The nature of AMD is complex and includes both environmental and hereditary factors. Oxidative stress is thought to be essential in AMD pathogenesis. Iron is suggested to be implicated in the pathogenesis of AMD through the catalysis of the production of reactive oxygen species, which can damage the retina. Heme oxygenase-2 is capable of degradation of heme producing free iron ions, thus, diversity in heme oxygenase-2 gene may contribute to AMD. In the present work we analyzed the association between the c.544G>A polymorphism of the heme oxygenase-2 gene (HMOX2) (rs1051308) and AMD. MATERIAL/METHODS: This study enrolled 276 AMD patients and 105 sex- and age-matched controls. Genotyping of the polymorphism was performed with restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) on DNA isolated from peripheral blood. RESULTS: We did not find any association between the genotypes of the c.544G>A polymorphism and the occurrence of AMD. This lack of association was independent of potential AMD risk factors: tobacco smoking, sex and age. Moreover, we did not find any association between AMD and smoking in our study population. CONCLUSIONS: The results suggest that the c.544G>A polymorphism of the heme oxygenase-2 gene is not associated with AMD in this Polish subpopulation.

The A Allele of the -576G>A polymorphism of the transferrin gene is associated with the increased risk of age-related macular degeneration in smokers.

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries, and its pathogenesis is underlined by genetic and environmental factors. Oxidative stress is a major environmental risk factor of AMD; namely, AMD is associated with the increased level of reactive oxygen species, which may be produced in reactions catalyzed by iron present in the retina. Therefore, variability of the genes of iron metabolism may be important in the AMD risk. In the present study, we analyzed the association between AMD and the -576G>A polymorphism of the transferrin gene or the 1892C>T polymorphism of the transferrin receptor 2 (TFR2) gene in 278 patients with AMD and 105 controls. The former polymorphism is located in the promoter region of the transferrin gene and may affect the level of its transcription, while the latter is a synonymous mutation in the exon 16, which may affect the efficiency of translation of TFR2 mRNA. Transferrin and TFR2 are important in iron homeostasis. The A allele of the -576A>G polymorphism was significantly associated with the increased risk of AMD in tobacco smokers, whereas the 1892C>T polymorphism did not influence the risk of AMD related to smoking. Moreover, each polymorphism does not influence the risk of AMD associated with age, sex or the family history of the disease. In conclusion, the A allele of the -576A>G polymorphism of the transferrin gene may increase the risk of AMD in smokers.

Immunology and Donor-Specific Antibodies in Corneal Transplantation.

The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients (e.g., vascularized or inflamed corneal tissue, consecutive transplants) remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring [e.g., donor-specific antibodies (DSA)] is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients.

The Association between Diabetes Mellitus and Keratoplasty in Poland in the Years 2013-2017.

BACKGROUND: The aim of this study is to assess the incidence and characteristic of corneal grafts and its association with diabetes mellitus in Poland in the years 2013-2017. METHODS: The retrospective survey of the National Database of Hospitalizations was performed to identify all the corneal transplantations in Poland between January 2013 and December 2017. The comorbid diseases, in particular diabetes mellitus, were verified in the patients' medical history. The logistic regression was applied to demonstrate the factors related to urgent surgeries. RESULTS: In total, 5069 corneal grafts in 4710 patients were reported in the years 2013-2017. The number of CTs gradually increased by 37% from 914 (2.37 surgeries per one hundred thousand population) in the year 2013 to 1250 (3.25 surgeries per one hundred thousand population) in 2017, the final year of the study. CT incidence was the highest in subjects aged 70 years or older: 13.18 per one hundred thousand population in the year 2017. On average, about 22.43% of procedures were performed in patients with DM. The chance of urgent surgery was mostly correlated with full thickness CT and patients' age. CONCLUSIONS: Despite the relatively low value of CT in Poland, there was an increasing number of CTs in the analyzed period.

Analysis of antioxidative factors related to AMD risk development in the polish patients.

PURPOSE: Age-related macular degeneration (AMD) is a major cause of blindness in developed countries. Oxidative mechanisms may play a key role in the aetiology of AMD. The main aim of this study was to investigate antioxidative markers in the pathogenesis of AMD. METHODS: A total of 510 subjects including 240 patients with AMD (mean age 77.9 ± 8.5 year) and 270 controls (mean age 74.0 ± 10.4 year) were allowed in this study. We measured activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and examined their association with the SNPs of respective genes (SOD1 + 35A/C, CAT C-262T and GPx Pro197Leu). Restriction fragment length polymorphism (RFLP) technique was used to determine the selected gene polymorphisms. Sixty subjects including 30 patients with AMD (mean age 69.4 ± 9.3) and 30 controls (mean age 64.6 ± 8.2) were enrolled to determine the activity of antioxidant enzymes by spectrometry method. RESULTS: A significant decrease in enzymes, SOD (p = 0.011), CAT (p = 0.002) and GPx (p ≤ 0.001) in AMD patients compared to controls, was indicated. The risk of susceptibility to AMD was significantly higher in patients with AMD who had Pro197Leu C/T genotype of GPx (OR = 2.78; 95% CI = 1.78-4.35). The A/C genotype and the C allele frequencies of A/C polymorphism of SOD1 gene significantly reduce the risk of AMD (OR=0.48; 95% CI 0.27; 0.85). CONCLUSION: In conclusion, our data showed that insufficient antioxidant capacity may have an important role in age-related macular degeneration. The polymorphism of GPx Pro197Leu may reduce the ability to scavenge free radicals in retina and contribute to the development of AMD.

Processing of OPA1 with a novel N-terminal mutation in patients with autosomal dominant optic atrophy: Escape from nonsense-mediated decay.

Autosomal Dominant Optic Atrophy (ADOA) is the most common dominantly inherited optic neuropathy. In the majority of patients it is caused by OPA1 mutations and those predicted to introduce a premature termination codon (PTC) are frequently detected. Transcripts containing PTC may be degraded by nonsense-mediated mRNA decay (NMD), however very little is known about an effect of OPA1 mutations on NMD activation. Here, using a combination of linkage analysis and DNA sequencing, we have identified a novel c.91C>T OPA1 mutation with a putative premature stop codon (Q31*), which segregated with ADOA in two Polish families. At the mRNA level we found no changes in the amount of OPA1 transcript among mutation carriers vs. non-carriers. Specific allele quantification revealed a considerable level of the OPA1 mutant transcript. Our study identifies a novel pathogenic OPA1 mutation and shows that it is located in the transcript region not prone for NMD activation. The data emphasizes the importance of analyzing how mutated genes are being processed in the cell. This gives an insight into the molecular mechanism of a genetic disease and promotes development of innovative therapeutic approaches.

Mapping cortical thickness of the patients with unilateral end-stage open angle glaucoma on planar cerebral cortex maps.

PURPOSE: To estimate and compare cerebral cortex thickness in patients with unilateral end-stage glaucoma with that of age-matched individuals with unaffected vision. METHODS: 14 patients with unilateral end-stage primary open angle glaucoma (POAG) and 12 age-matched control individuals with no problems with vision were selected for the study based on detailed ophthalmic examination. For each participant 3D high-resolution structural brain T1-weighted magnetization prepared MR images were acquired on a 3.0 T scanner. Brain cortex thickness was estimated using the FreeSurfer image analysis environment. After warping of subjects' cortical surfaces to FreeSurfer common space, differences between POAG and control groups were inferred at the group analysis level with the General Linear Model. RESULTS: The analysis performed revealed local thinning in the visual cortex areas in the POAG group. Statistically significant differences form 600 mm2 clusters located in the Brodmann area BA19 in the left and right hemisphere. CONCLUSION: Unilateral vision loss due to end-stage neuropathy from POAG is associated with significant thinning of cortical areas employed in vision.

Variability of the transferrin receptor 2 gene in AMD.

Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Iron may catalyze the Fenton reaction resulting in overproduction of reactive oxygen species. Transferrin receptor 2 plays a critical role in iron homeostasis and variability in its gene may influence oxidative stress and AMD occurrence. To verify this hypothesis we assessed the association between polymorphisms of the TFR2 gene and AMD. A total of 493 AMD patients and 171 matched controls were genotyped for the two polymorphisms of the TFR2 gene: c.1892C>T (rs2075674) and c.-258+123T>C (rs4434553). We also assessed the modulation of some AMD risk factors by these polymorphisms. The CC and TT genotypes of the c.1892C>T were associated with AMD occurrence but the latter only in obese patients. The other polymorphism was not associated with AMD occurrence, but the CC genotype was correlated with an increasing AMD frequency in subjects with BMI < 26. The TT genotype and the T allele of this polymorphism decreased AMD occurrence in subjects above 72 years, whereas the TC genotype and the C allele increased occurrence of AMD in this group. The c.1892C>T and c.-258+123T>C polymorphisms of the TRF2 gene may be associated with AMD occurrence, either directly or by modulation of risk factors.