ORCID Profile
0000-0002-0353-7415
Current Organisations
Hospital de Clínicas de Porto Alegre
,
Universidade Federal do Rio Grande do Sul
,
University of Toronto
,
Grupo Hospitalar Conceição
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2021
DOI: 10.1097/APO.0000000000000371
Abstract: The management of noninfectious uveitis is constantly evolving. A new “biologic era” in treatment began after the effectiveness of tumor necrosis factor-alpha blocking drugs was demonstrated in rheumatologic inflammatory diseases. The goal of specific immunomodulation with a biologic drug is to target inflammation at the molecular level with a low rate of serious adverse events. The purpose of this review is to summarize current knowledge of biologic drugs in the treatment of noninfectious uveitis by describing clinical studies and recent pharmacological developments.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2023
DOI: 10.1186/S12348-023-00341-6
Abstract: Interleukin (IL)-6 is an inflammatory cytokine present in the eye during non-infectious uveitis, where it contributes to the progression of inflammation. There are two major IL-6 signaling pathways: classic signaling and trans-signaling. Classic signaling requires cellular expression of the IL-6 receptor (IL-6R), which exists in membrane-bound (mIL-6R) and soluble (sIL-6R) forms. Prevailing dogma is that vascular endothelial cells do not produce IL-6R, relying on trans-signaling during inflammation. However, the literature is inconsistent, including with respect to human retinal endothelial cells. We examined IL-6R transcript and protein expression in multiple primary human retinal endothelial cell isolates, and assessed the effect of IL-6 on the transcellular electrical resistance of monolayers. Using reverse transcription-polymerase chain reaction, IL-6R, mIL-6R and sIL-6R transcripts were lified in 6 primary human retinal endothelial isolates. Flow cytometry on 5 primary human retinal endothelial cell isolates under non-permeabilizing conditions and following permeabilization demonstrated intracellular stores of IL-6R and the presence of mIL-6R. When measured in real-time, transcellular electrical resistance of an expanded human retinal endothelial cell isolate, also shown to express IL-6R, decreased significantly on treatment with recombinant IL-6 in comparison to non-treated cells across 5 independent experiments. Our findings indicate that human retinal endothelial cells produce IL-6R transcript and functional IL-6R protein. The potential for classic signaling in human retinal endothelial cells has implications for the development of therapeutics targeted against IL-6-mediated pathology in non-infectious uveitis.
Publisher: MDPI AG
Date: 28-01-2022
DOI: 10.3390/MICROORGANISMS10020310
Abstract: Prevalence of dengue retinopathy varies across epidemics, with the disease linked to circulation of dengue virus serotype 1 (DENV-1). The retinal pigment epithelium has been implicated in the pathology. We investigated infectivity, molecular response, and barrier function of epithelial cells inoculated with DENV strains from different outbreaks in Singapore. Monolayers of human retinal pigment epithelial cells (multiple primary cell isolates and the ARPE-19 cell line) were inoculated with six DENV strains, at multiplicity of infection of 10 uninfected and recombinant strain-infected controls were included where relevant. Infectivity and cell response were assessed primarily by RT-qPCR on total cellular RNA, and barrier function was evaluated as electrical resistance across monolayers. Higher viral RNA loads were measured in human retinal pigment epithelial cells infected with DENV-1 strains from the 2005 Singapore epidemic, when retinopathy was prevalent, versus DENV-1 strains from the 2007 Singapore epidemic, when retinopathy was not observed. Type I interferon (IFN) transcripts (IFN-β and multiple IFN-stimulated genes) were up-regulated, and impact on barrier function was more pronounced, for cells infected with DENV-1 strains from the 2005 versus the 2007 Singapore epidemics. Aside from serotype, strain of DENV may determine the potential to induce retinal pathology. Identification of molecular markers of disease-associated DENV strains may provide insights into the pathogenesis of dengue retinopathy.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.ORET.2022.04.022
Abstract: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study. Cross-sectional, community-based, prospective cohort study. 5020 Australian adults (2264 men and 2756 women age range, 45-69 years, and median age, 58 years). Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis. Prevalence of toxoplasmic retinochoroiditis. Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021 :3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67% or 1 per 149 persons. Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified.
Publisher: Frontiers Media SA
Date: 07-03-2023
DOI: 10.3389/FMED.2023.1128811
Abstract: Macular edema is the pathological accumulation of fluid in the central retina. It is a complication of many retinal diseases, including diabetic retinopathy, retinal vascular occlusions and uveitis, among others. Macular edema causes decreased visual acuity and, when chronic or refractory, can cause severe and permanent visual impairment and blindness. In most instances, it develops due to dysregulation of the blood-retinal barrier which permits infiltration of the retinal tissue by proteins and other solutes that are normally retained in the blood. The increase in osmotic pressure in the tissue drives fluid accumulation. Current treatments include vascular endothelial growth factor blockers, corticosteroids, and non-steroidal anti-inflammatory drugs. These treatments target vasoactive and inflammatory mediators that cause disruption to the blood-retinal barrier. In this review, a clinical overview of macular edema is provided, mechanisms of disease are discussed, highlighting processes targeted by current treatments, and areas of opportunity for future research are identified.
Publisher: FapUNIFESP (SciELO)
Date: 12-2009
DOI: 10.1590/S0004-282X2009000600021
Abstract: There are no published studies on the characteristics of multiple sclerosis (MS) patients from the south of Brazil. OBJECTIVE: To identify the clinical features of a series of MS patients and to compare to other Brazilian series. METHOD: Retrospective study with 67 patients followed in The MS Reference Center - RS, Brazil during the year of 2008. We analyzed demographic and clinical data. RESULTS: Most were women (74.6%), the general average age was 43.5 years old, and the general average EDSS score was 4.1. Of those patients, 81.8% had relapsing-remitting MS. Sexual dysfunction prevalence was 31.1% in men and 68.9% in women (p .01). We found a positive correlation (Spearman=0.444, p .05) between EDSS and depressive symptoms. CONCLUSION: This study showed a very similar s le compared to other states of Brazil. Moreover, there was found a high prevalence of sexual dysfunction and a straight relation between EDSS and depressive symptoms.
Publisher: GN1 Sistemas e Publicacoes Ltd.
Date: 2021
Publisher: Informa UK Limited
Date: 04-10-2022
DOI: 10.1080/09273948.2022.2122512
Abstract: Retinal endothelial cell activation is a central event in non-infectious posterior uveitis. There is recent interest in long non-coding (lnc)RNA-targeted therapeutics for retinal diseases. We aimed to identify human retinal endothelial cell lncRNAs that might be involved in activation. Eleven candidate lncRNAs were identified: GAS5, KCNQ1OT1, LINC00294, MALAT1, MEG3, MIR155HG, NEAT1, NORAD, OIP5-AS1, SENCR, TUG1. Expression was assessed by RT-PCR in human retinal endothelial cells, at baseline and following activation with interleukin (IL)-1β and tumor necrosis factor (TNF)-α. IL-1β significantly upregulated MEG3 and SENCR at 4 and 24 hours LINC00294, NORAD, OIP5-AS1 and TUG1 at 24 hours and MIR155HG at 4, 24 and 48 hours but downregulated GAS5 at 24 and 48 hours. TNF-α significantly upregulated KCNQ1OT1, LINC00294, MEG3, NORAD and SENCR at 4 hours SENCR and TUG1 at 24 hours and MIR155HG at all time points. Future studies involving manipulation of MIR155HG may be warranted to explore potential therapeutic applications for non-infectious posterior uveitis.
Publisher: Springer Science and Business Media LLC
Date: 21-01-2022
DOI: 10.1038/S41598-022-05070-9
Abstract: Toxoplasmic retinochoroiditis is a common, potentially blinding parasitic infection. We sought to define the spectrum and frequency of signs of active toxoplasmic retinochoroiditis by spectral domain optical coherence tomography (SD-OCT), and to identify clinical associations. Ninety eyes of 90 in iduals presenting consecutively to a tertiary referral uveitis service with active toxoplasmic retinochoroiditis and gradable SD-OCT scans were evaluated prospectively. SD-OCT features were collated, and associations with lesion location, primary versus recurrent episode, serological status, human immunodeficiency virus infection and best-corrected Snellen visual acuity were explored. Active toxoplasmic retinochoroiditis presented with thickened (65%) and hyperreflective (61%) retina, choroidal thickening (55%) and hyporeflectivity (61%), hyperreflective vitreous dots (80%) and deposits (36%), and posterior hyaloid thickening (35%) on SD-OCT. Most signs occurred with similar frequency across clinical groups. Retinal hyporeflectivity (17%) was significantly associated with a visual acuity of 20/200 or worse at resolution. Our observations demonstrate that active toxoplasmic retinochoroiditis has erse SD-OCT signs and that none are universally present. Retinal hyporeflectivity—suggesting liquefactive necrosis—predicts poor visual outcome.
No related grants have been discovered for Lisia Barros Ferreira.