Widespread Protection of RNA Cleavage Sites by a Riboswitch Aptamer that Folds as a Compact Obstacle to Scanning by RNase E.

Riboswitches are thought generally to function by modulating transcription elongation or translation initiation. In rare instances, ligand binding to a riboswitch has been found to alter the rate of RNA degradation by directly stimulating or inhibiting nearby cleavage. Here, we show that guanidine-induced pseudoknot formation by the aptamer domain of a guanidine III riboswitch from Legionella pneumophila has a different effect, stabilizing mRNA by protecting distal cleavage sites en masse from ribonuclease attack. It does so by creating a coaxially base-paired obstacle that impedes scanning from a monophosphorylated 5' end to those sites by the regulatory endonuclease RNase E. Ligand binding by other riboswitch aptamers peripheral to the path traveled by RNase E does not inhibit distal cleavage. These findings reveal that a riboswitch aptamer can function independently of any overlapping expression platform to regulate gene expression by acting directly to prolong mRNA longevity in response to ligand binding.

Riboswitch-Associated Guanidinium-Selective Efflux Pumps Frequently Transmitted on Proteobacterial Plasmids Increase Escherichia coli Biofilm Tolerance to Disinfectants.

Members of the small multidrug resistance (SMR) efflux pump family known as SugE (recently renamed Gdx) are known for their narrow substrate selectivity to small guanidinium (Gdm+) compounds and disinfectant quaternary ammonium compounds (QACs). Gdx members have been identified on multidrug resistance plasmids in Gram-negative bacilli, but their functional role remains unclear, as few have been characterized. Here, we conducted a survey of sequenced proteobacterial plasmids that encoded one or more SugE/Gdx sequences in an effort to (i) identify the most frequently represented Gdx member(s) on these plasmids and their sequence diversity, (ii) verify if Gdx sequences possess a Gdm+ riboswitch that regulates their translation similarly to chromosomally encoded Gdx members, and (iii) determine the antimicrobial susceptibility profile of the most predominate Gdx member to various QACs and antibiotics in Escherichia coli strains BW25113 and KAM32. The results of this study determined 14 unique SugE sequences, but only one Gdx sequence, annotated as "SugE(p)," predominated among the >140 plasmids we surveyed. Enterobacterales plasmids carrying sugE(p) possessed a guanidine II riboswitch similar to the upstream region of E. coligdx Cloning and expression of sugE(p), gdx, and emrE sequences into a low-copy-number expression vector (pMS119EH) revealed significant increases in QAC resistance to a limited range of detergent-like QACs only when gdx and sugE(p) transformants were grown as biofilms. These findings suggest that sugE(p) presence on proteobacterial plasmids may be driven by species that frequently encounter Gdm+ and QAC exposure.IMPORTANCE This study characterized the function of antimicrobial-resistant phenotypes attributed to plasmid-encoded guanidinium-selective small multidrug resistance (Gdm/SugE) efflux pumps. These sequences are frequently monitored as biocide resistance markers in antimicrobial resistance surveillance studies. Our findings reveal that enterobacterial gdm sequences transmitted on plasmids possess a guanidine II riboswitch, which restricts transcript translation in the presence of guanidinium. Cloning and overexpression of this gdm sequence revealed that it confers higher resistance to quaternary ammonium compound (QAC) disinfectants (which possess guanidium moieties) when grown as biofilms. Since biofilms are commonly eradicated with QAC-containing compounds, the presence of this gene on plasmids and its biofilm-specific resistance are a growing concern for clinical and food safety prevention measures.

GdX/UBL4A null mice exhibit mild kyphosis and scoliosis accompanied by dysregulation of osteoblastogenesis and chondrogenesis.

GdX, also named ubiquitin-like protein 4A, is a ubiquitin-domain protein characterized by a ubiquitin-like domain that regulates the movement of misfolded proteins from the endoplasmic reticulum membrane to proteasome. However, its function in skeletal biology remains unclear. Here, we report that GdX plays a crucial role in skeletal development as mice lacking GdX exhibit skeletal dysplasias, mild kyphosis, and scoliosis. During embryonic stage, GdX knockout mice display decreased bone mineral density and trabecular bone accompanied by delayed osteogenic formation. GdX knockout mice also have blended spine and small body size. At the molecular level, GdX knockout mice showed perturbed expression of osteogenesis-related genes and cartilage developmental genes, indicative of altered differentiation of mesenchymal cell lineage. Collectively, our results uncovered GdX as a novel regulator in bone development and a potential candidate gene for skeletal dysplasias.

Sex differences in circadian timing systems: implications for disease.

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.

Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products.

Metformin is used globally to treat type II diabetes, has demonstrated anti-ageing and COVID mitigation effects and is a major anthropogenic pollutant to be bioremediated by wastewater treatment plants (WWTPs). Metformin is not adsorbed well by activated carbon and toxic N-chloro derivatives can form in chlorinated water. Most earlier studies on metformin biodegradation have used wastewater consortia and details of the genomes, relevant genes, metabolic products, and potential for horizontal gene transfer are lacking. Here, two metformin-biodegrading bacteria from a WWTP were isolated and their biodegradation characterized. Aminobacter sp. MET metabolized metformin stoichiometrically to guanylurea, an intermediate known to accumulate in some environments including WWTPs. Pseudomonas mendocina MET completely metabolized metformin and utilized all the nitrogen atoms for growth. Pseudomonas mendocina MET also metabolized metformin breakdown products sometimes observed in WWTPs: 1-N-methylbiguanide, biguanide, guanylurea, and guanidine. The genome of each bacterium was obtained. Genes involved in the transport of guanylurea in Aminobacter sp. MET were expressed heterologously and shown to serve as an antiporter to expel the toxic guanidinium compound. A novel guanylurea hydrolase enzyme was identified in Pseudomonas mendocina MET, purified, and characterized. The Aminobacter and Pseudomonas each contained one plasmid of 160 kb and 90 kb, respectively. In total, these studies are significant for the bioremediation of a major pollutant in WWTPs today.

Comparison of imaging parameters between OCT, GDx and HRT in the Northern Finland birth cohort eye study.

PURPOSE: The purpose of the study was to assess and compare the optic nerve head (ONH) and retinal nerve fibre layer (RNFL) parameters and image quality parameters obtained by Cirrus HD-OCT, GDxECC and HRT3 in a population-based screening study. METHODS: This analysis examined 2566 subjects taking part in the Northern Finland Birth Cohort Eye study. Images with spectral domain OCT (Cirrus HD-OCT 4000), scanning laser ophthalmoscopy (HRT3) and scanning laser polarimetry (GDxECC) were obtained from each subject. The correlation of average and regional parameters of RNFL and ONH between devices was evaluated. RESULTS: The RNFL thickness was 90.9 µm when measured with OCT, 24.6 µm with HRT and 48.1 µm with GDx. There was a high correlation between the disc and cup measurements with the HRT and OCT and the RNFL thickness of the OCT and GDx (r > 0.5). A statistically significant correlation was found between RNFL measurements of the HRT and OCT in the superior, temporal and inferior quadrants. Optical coherence tomography (OCT) signal strength correlated with the image quality parameters of the HRT and GDx. The percentage of good quality images was the lowest with the GDx. CONCLUSION: The RNFL thickness in Northern Finland birth cohort was at a lower level compared to other studies. The study confirms the difference in measuring ONH parameters between the imaging devices. However, significant correlations between devices were found in the cup volume and cup disc area ratio parameters of the OCT and HRT. The correlations between image quality parameters and glaucoma detection parameters were relatively low.

Diagnostic performance of modern imaging instruments in glaucoma screening.

AIM: To evaluate the applicability of imaging devices (spectral-domain optical coherence tomography (Cirrus SD-OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (Heidelberg Retinal Tomograph, HRT3)) for glaucoma screening in a middle-aged unselected population. METHODS: Participants of the population-based Northern Finland Birth Cohort Eye Study, aged 45 to 49 years, underwent a comprehensive eye examination including modern imaging with five methods (retinal nerve fibre layer (RNFL) and macular ganglion cell layer +inner plexiform layer (GCIPL) analysis and their combination with SD-OCT, GDx and HRT). The performance of the automated classification of the imaging devices was assessed using a clinical glaucoma diagnosis as reference, that is, the '2 out of 3' rule based on the evaluation of optic nerve head and RNFL photographs and visual fields. RESULTS: We examined 6060 eyes of 3039 subjects; in the clinical evaluation, glaucomatous damage was found in 33 subjects (1.1%) in 43 eyes. The following sensitivities were obtained; RNFL analysis (53%), GCIPL analysis (50%), OCT combination analysis (61%), GDx (56%) and HRT (31%) with corresponding specificities of 95%, 92%, 90%, 88% and 96%. The area under the curve values were 0.76, 0.73, 0.75, 0.75 and 0.73, respectively. Post-test probabilities of glaucoma after positive imaging finding with each of these methods in this unselected population were 11%, 7%, 6%, 5% and 7%, respectively. CONCLUSION: Screening capabilities of the OCT, GDx and HRT were rather similar. The accuracy of all evaluated parameters was only moderate and thus screening with these parameters alone is not reliable.

Absence of GdX/UBL4A Protects against Inflammatory Diseases by Regulating NF-кB Signaling in Macrophages and Dendritic Cells.

Nuclear factor-kappa B (NF-κB) activation is critical for innate immune responses. However, cellular-intrinsic regulation of NF-κB activity during inflammatory diseases remains incompletely understood. Ubiquitin-like protein 4A (UBL4A, GdX) is a small adaptor protein involved in protein folding, biogenesis and transcription. Yet, whether GdX has a role during innate immune response is largely unknown. Methods: To investigate the involvement of GdX in innate immunity, we challenged GdX-deficient mice with lipopolysaccharides (LPS). To investigate the underlying mechanism, we performed RNA sequencing, real-time PCR, ELISA, luciferase reporter assay, immunoprecipitation and immunoblot analyses, flow cytometry, and structure analyses. To investigate whether GdX functions in inflammatory bowel disease, we generated dendritic cell (DC), macrophage (Mφ), epithelial-cell specific GdX-deficient mice and induced colitis with dextran sulfate sodium. Results: GdX enhances DC and Mφ-mediated innate immune defenses by positively regulating NF-κB signaling. GdX-deficient mice were resistant to LPS-induced endotoxin shock and DSS-induced colitis. DC- or Mφ- specific GdX-deficient mice displayed alleviated mucosal inflammation. The production of pro-inflammatory cytokines by GdX-deficient DCs and Mφ was reduced. Mechanistically, we found that tyrosine-protein phosphatase non-receptor type 2 (PTPN2, TC45) and protein phosphatase 2A (PP2A) form a complex with RelA (p65) to mediate its dephosphorylation whereas GdX interrupts the TC45/PP2A/p65 complex formation and restrict p65 dephosphorylation by trapping TC45. Conclusion: Our study provides a mechanism by which NF-κB signaling is positively regulated by an adaptor protein GdX in DC or Mφ to maintain the innate immune response. Targeting GdX could be a strategy to reduce over-activated immune response in inflammatory diseases.

Follow-up of the retinal nerve fiber layer thickness of diabetic patients type 2, as a predisposing factor for glaucoma compared to normal subjects.

PURPOSE: To evaluate and follow-up the retinal nerve fiber layer (RNFL) thickness in patients with diabetes mellitus type 2 compared to a group of healthy individuals with similar demographic characteristics. PATIENTS AND METHODS: This is a prospective, noninvasive, observational case series study. For the purposes of the study, 27 eyes of diabetic patients without diabetic retinopathy, 24 eyes of patients with mild retinopathy, and 25 normal age-matched subjects (control group [CG]) were examined. All participants underwent complete ophthalmological examination and imaging with GDx variable corneal compensation scanning laser polarimetry. Follow-up was 2 years for all three groups. RESULTS: The mean inferior average was statistically significantly lower in both diabetic groups compared to CG at baseline examination and during follow-up. The nerve fiber indicator (NFI) was higher in both diabetic groups compared to CG, both at baseline examination and during follow-up. The NFI was 21.7±11.9 and 22.0±11.8 for the diabetic group without retinopathy, 20.8±9.6 and 21.9±9.8 for the group with mild retinopathy, and 15.3±5.4 and 15.9±5.5 for the normal subjects, at baseline and 24 months, respectively. There was no statistically significant reduction of the RNFL thickness in all three groups compared to baseline examination. CONCLUSION: This is the first long-term study documenting the RNFL thickness in diabetic patients in comparison with normal controls. Although the lower RNFL was found thinner in diabetics, the 2-year follow-up showed no significant reduction of RNFL thickness in all groups, indicating that RNFL damage may occur early in diabetic patients.

New model for prediction binary mixture of antihistamine decongestant using artificial neural networks and least squares support vector machine by spectrophotometry method.

In the present study, artificial neural networks (ANNs) and least squares support vector machines (LS-SVM) as intelligent methods based on absorption spectra in the range of 230-300nm have been used for determination of antihistamine decongestant contents. In the first step, one type of network (feed-forward back-propagation) from the artificial neural network with two different training algorithms, Levenberg-Marquardt (LM) and gradient descent with momentum and adaptive learning rate back-propagation (GDX) algorithm, were employed and their performance was evaluated. The performance of the LM algorithm was better than the GDX algorithm. In the second one, the radial basis network was utilized and results compared with the previous network. In the last one, the other intelligent method named least squares support vector machine was proposed to construct the antihistamine decongestant prediction model and the results were compared with two of the aforementioned networks. The values of the statistical parameters mean square error (MSE), Regression coefficient (R2), correlation coefficient (r) and also mean recovery (%), relative standard deviation (RSD) used for selecting the best model between these methods. Moreover, the proposed methods were compared to the high- performance liquid chromatography (HPLC) as a reference method. One way analysis of variance (ANOVA) test at the 95% confidence level applied to the comparison results of suggested and reference methods that there were no significant differences between them.

Imaging of the optic disk in caring for patients with glaucoma: ophthalmoscopy and photography remain the gold standard.

Optic disk imaging is integral to the diagnosis and treatment of patients with glaucoma. We discuss the various forms of imaging the optic nerve, including ophthalmoscopy, photography, and newer imaging modalities, including optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (HRT), and scanning laser polarimetry (GDx), specifically highlighting their benefits and disadvantages. We argue that ophthalmoscopy and photography remain the gold standard of imaging due to portability, ease of interpretation, and the presence of a large database of images for comparison.

Annexin A1 is regulated by domains cross-talk through post-translational phosphorylation and SUMOYlation.

Mouse prostate membrane-associated proteins of the annexin family showed changes in SUMOylation during androgen treatment. Among these the calcium-binding annexin A1 protein (ANXA1) was chosen for further characterization given its role in protein secretion and cancer. SUMOylation of ANXA1 was confirmed by overexpressing SUMO-1 in LNCaP cells. Site-directed mutagenesis indicated that K257 located in a SUMOylation consensus motif in the C-terminal calcium-binding DA3 repeat domain is SUMOylated. Mutation of the N-terminal Y21 decreased markedly the SUMOylation signal while EGF stimulation increased ANXA1 SUMOylation. A structural analysis of ANXA1 revealed that K257 is located in a hot spot where Ca(2+) and SUMO-1 bind and where a nuclear export signal and a polyubiquitination site are also present. Also, Y21 is buried inside an α-helix structure in the Ca(2+)-free conformation implying that Ca(2+) binding, and the subsequent expelling of the N-terminal α-helix in a disordered conformation, is permissive for its phosphorylation. These results show for the first time that SUMOylation can be regulated by an external signal (EGF) and indicate the presence of a cross-talk between the N-terminal and C-terminal domains of ANXA1 through post-translational modifications.

Structural and functional relationships in glaucoma using standard automated perimetry and the Humphrey Matrix.

PURPOSE: To evaluate and compare correlations between structural and functional loss in glaucoma as assessed by optical coherence tomography (OCT), scanning laser polarimetry (GDx VCC, as this was the model used in this study), standard automated perimetry (SAP), and the Humphrey Matrix (Matrix). METHODS: Ninety glaucomatous eyes identified with SAP and 112 eyes diagnosed using Matrix were independently classified into six subgroups, either S1/M1 (MD>-6dB), S2/M2 (-12

Longitudinal Analysis of Retinal Nerve Fiber Layer Thickness With GDx-VCC in Glaucoma Suspect

PURPOSE: The changes of retinal nerve fiber layer thickness with GDx-VCC were analyzed to assess the use of this instrument for longitudinal follow-up of retinal nerve fiber layers. METHODS: From July 2004 to July 2007, patients suspected of glaucoma were measured with GDx-VCC at baseline and measurements were repeated at a minimum interval of 12 months. The medical records of 150 patients were reviewed and 42 patients that showed glaucomatous visual field progression in 36 months were classified into a "progression group" and 108 patients with no visual field loss were classified into a "nonprogression group". RESULTS: In the nonprogression group, the temporal superior-nasal-inferior-temporal (TSNIT) average and theinferior average showed statistically significant changes for the follow up periods. However, in theprogression group, there were no parameters with significant changes even though glaucomatous visual field loss was found. The visual field progressed at a rate of 0.1dB/year in the progression group but the relationship between MD, PSD and GDx-VCC parameters could not be established. CONCLUSIONS: GDx-VCC may not be sufficient for longitudinal assessment of the RNFL, especially during the early glaucomatous visual field changes. The progression of glaucoma only with GDx-VCC should be cautiously evaluated, and confirmation with the visual field which elucidates early glaucomatous changes is necessary. Further study is needed before GDx-VCC can be recommended as the instrument for longitudinal assessment.

Structural and Functional Relationships in Glaucoma Using Standard Automated Perimetry and the Humphrey Matrix

PURPOSE: To evaluate and compare correlations between structural and functional loss in glaucoma as assessed by optical coherence tomography (OCT), scanning laser polarimetry (GDx VCC, as this was the model used in this study), standard automated perimetry (SAP), and the Humphrey Matrix (Matrix). METHODS: Ninety glaucomatous eyes identified with SAP and 112 eyes diagnosed using Matrix were independently classified into six subgroups, either S1/M1 (MD>-6dB), S2/M2 (-12

Relationship between Scanning Laser Polarimetry with Enhanced Corneal Compensation and with Variable Corneal Compensation

PURPOSE: To evaluate the structure-function relationships between retinal sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP) with variable corneal compensation (VCC) and enhanced corneal compensation (ECC) in glaucomatous and healthy eyes. METHODS: Fifty-three eyes with an atypical birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was measured by both VCC and ECC techniques, and the visual field was examined by HVFA with 24-2 full-threshold program. The relationships between RNFL measurements in superior and inferior sectors and corresponding retinal mean sensitivity were sought globally and regionally with linear regression analysis in each group. Coefficients of the determination were calculated and compared between VCC and ECC techniques. RESULTS: In eyes with ABP, R2 values for the association between SLP parameters and retinal sensitivity were 0.06-0.16 with VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8 regression models between SLP parameters and HVF parameters (P<0.05). CONCLUSIONS: The strength of the structure-function association was higher with ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a better approach for evaluating the structure-function relationship in eyes with ABP.

Changes in RNFL Thickness According to the Myopia in Patients with Glaucoma and Ocular Hypertension

PURPOSE: To evaluate the changes in retinal nerve fiber layer (RNFL) thickness according to the degree of myopia in patients with glaucoma and ocular hypertension. METHODS: Ninety-eight patients (165 eyes) diagnosed with glaucoma or ocular hypertension underwent optical coherence tomography (OCT) and scanning laser polarimetry using variable corneal compensation (GDx-VCC) to analyze the correlation between the degree of myopia and the thickness of the RNFL. A partial correlation coefficient analysis was performed to adjust for various factors such as age, laterality, intraocular pressure, and the mean deviation from visual field test, which can influence the RNFL thickness. RESULTS: The average, nasal, superior, and inferior sectorial RNFL thicknesses measured by OCT significantly decreased with increasing myopia (p<0.05). However, RNFL thickness measured by GDx-VCC was not significantly correlated with the degree of myopia. CONCLUSIONS: The RNFL thickness measured by OCT decreased with increasing myopia in eyes with glaucoma and ocular hypertension.

Diagnostic Ability of Scanning Laser Polarimetry with Enhanced Corneal Compensation in the Eye with Typical and Atypical Retadation Pattern

PURPOSE: To investigate the relationship between the SLP-VCC parameters and the SLP-ECC parameters in the eyes with typical retardation pattern (TRP) and atypical retardation pattern (ARP), and the sensitivities and specificities of the SLP-VCC parameters and the SLP-ECC parameters in the eye with TRP and ARP. METHODS: In this prospective study, 72 eyes with TRP images (30 glaucomatous and 42 normal eyes) and 53 eyes with ARP images (28 glaucomatous and 25 normal eyes) were recruited. For each group, we analyzed relationship between each parameters of GDx-VCC and GDx-ECC and the diagnostic ability of GDx-ECC by using the ROC curve. RESULTS: In the eyes with TRP, TSNIT average was significantly lower by GDx-ECC than GDx-VCC in the control group. Inferior average was significantly higher by GDx-ECC than GDx-VCC in both glaucomatous and normal group. TSNIT standard deviation was significantly higher by GDx-ECC than GDx-VCC in both groups. NFI was significantly lower by GDx-ECC than GDx-VCC in both groups. TSS (typical scan score) was significantly higher by GDx-ECC than GDx-VCC in both groups. In the eyes with ARP, TSNIT average was significantly lower by GDx-ECC than GDx-VCC in both groups. Superior and Inferior average was not different between GDx-ECC and GDx-VCC. TSNIT standard deviation was significantly higher by GDx-ECC than GDx-VCC in both groups. NFI was not different between groups. TSS was significantly higher by GDx-ECC than GDx-VCC in both groups. Comparison of ROC curve for the SLP parameters revealed no difference between VCC and ECC. TSNIT standard deviation, however, showed relatively high value in GDx-ECC compared with GDx-VCC. CONCLUSIONS: GDx-ECC has comparable diagnostic ability in discriminating glaucomatous and normal eyes with GDx-VCC and TSNIT standard deviation by the GDx-ECC algorithm could be a useful parameter in discriminating glaucomatous and normal eyes.

GDx-VCC Performance to Discriminate Normal, Pre-perimetric Glaucomatous Eyes

PURPOSE: This study was designed to assess the diagnostic value of scanning laser polarimetry with variable corneal compensation (GDx-VCC) in the diagnosis of preperimetric glaucoma. METHODS: The study included 132 eyes of 132 patients with normal intraocular pressure, including 38 normal eyes, 60 eyes with pre-perimetric glaucoma, and 34 eyes with early glaucoma. The parameters of GDx-VCC were analyzed and compared in these groups using ANOVA. The parameter with the most powerful diagnostic value was defermirred by an ROC curve, and it's sensitivity and specificity were calculated. RESULTS: Among GDx-VCC parameters, NFI was the most valuable parameter that could detect pre-perimetric glaucoma in normal eyes. A cut-off value of 12 was the optimal NFI value, which offered the highest sensitivity and specificity in discriminating between normal and pre-perimetric glaucomatous eyes. However, there were no statistically significant differences in GDx-VCC parameters between pre-perimetric and early glaucomatous eyes. A statistically significant correlation was found between NFI and visual field indices in early glaucomatous eyes. CONCLUSIONS: GDx-VCC can be useful as a screening test for early detection of pre-perimetric and early glaucoma with normal intraocular pressure.

Achados oftalmológicos em pacientes que receberam transplante cardíaco / Ophthalmologic findings in cardiac transplant recipients

OBJETIVO: Avaliar os achados oculares, pelo exame oftalmológico, em indivíduos que receberam transplante cardíaco, buscando especialmente investigar possíveis alterações na camada de fibras nervosas da retina com polarímetro de varredura a laser. MÉTODOS: Foram estudados 15 indivíduos que receberam transplante cardíaco no período de setembro de 2003 a julho de 2004. Todos foram submetidos a exame que constava de acuidade visual para longe (AVL), biomicroscopia, tonometria e fundoscopia. Onze pacientes foram submetidos ao analisador de fibras nervosas GDx. Doze eram do sexo masculino e a média da idade foi de 55,0 ± 13,5 anos. O tempo decorrido desde o transplante variou de 3 a 74 meses, com média de 29,7 ± 20,8 meses. RESULTADOS: A AVL com melhor correção foi igual ou melhor do que 20/40 em todos os pacientes. Em um deles observou-se a presença de catarata subcapsular posterior; em outro, nubéculas na córnea secundárias a quadro de herpes zoster. À fundoscopia pôde-se observar lesão cicatrizada sugestiva de retinocoroidite em um paciente. As alterações observadas à biomicroscopia e à fundoscopia eram esperadas devido à imunossupressão subseqüente ao transplante. Ao GDx observou-se perda de fibras da camada de fibras nervosas da retina superior em 12 dos 22 olhos avaliados. CONCLUSÃO: Os resultados apóiam a suposição de que antes ou durante o transplante cardíaco tenha havido diminuição no aporte de oxigênio à circulação retiniana, levando a perda parcial de fibras da retina.

PURPOSE: To evaluate findings of ophthalmologic examinations in cardiac transplant recipients, searching especially for changes in the retinal nerve fiber layer by means of Scanning Laser Polarimetry. METHODS: Fifteen cardiac transplant recipients were examined from September 2003 to July 2004. All of them underwent ophthalmologic examination, which consisted of visual acuity (VA), biomicroscopy, tonometry and fundoscopy. Fiber layer analyzer - GDx - examination was performed in eleven patients. Twelve patients were men. The mean age was 55.0 ± 13.5 years. The follow-up since transplantation lasted from 3 to 74 months; mean value 29.7 ± 20.8 months. RESULTS: VA with best correction in all patients attained at least 20/40. Subcapsular posterior cataract was seen in one patient; another presented corneal nubeculae secondary to herpes zoster. In one case a scar suggesting retinocoroiditis was seen at fundoscopy. Biomicroscopic and the fundoscopic findings were expected because of immunosuppressive treatment, following transplantation. GDx examination disclosed loss of fibers in the superior retinal fiber layer in 12 of the 22 examined eyes. CONCLUSION: These results support the hypothesis that reduction of oxygen inflow in retinal circulation before or during heart transplantation could lead to loss of fibers in the retinal nerve fiber layer.