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Journal of Clinical Medicine Aug 2023Proliferative vitreoretinopathy (PVR) remains the main cause of failure after retinal detachment (RD) surgery. Despite the development of modern technologies and... (Review)
Review
Proliferative vitreoretinopathy (PVR) remains the main cause of failure after retinal detachment (RD) surgery. Despite the development of modern technologies and sophisticated techniques for the management of RD, the growth of fibrocellular membranes within the vitreous cavity and on both sides of the retinal surface, as well as intraretinal fibrosis, can compromise surgical outcomes. Since 1983, when the term PVR was coined by the Retina Society, a lot of knowledge has been obtained about the physiopathology and risk factors of PVR, but, despite the proposal of a lot of therapeutic challenges, surgical skills seem to be the only effective way to manage PVR complications.
PubMed: 37629329
DOI: 10.3390/jcm12165287 -
Clinical Ophthalmology (Auckland, N.Z.) 2023Lattice degeneration (LD), routinely diagnosed with indirect ophthalmoscopy, is one of the most common and clinically significant peripheral retinal findings. In this... (Review)
Review
Lattice degeneration (LD), routinely diagnosed with indirect ophthalmoscopy, is one of the most common and clinically significant peripheral retinal findings. In this review, we have summarized the data on currently available imaging techniques which help to improve diagnosis and our understanding of LD pathogenesis. Ultra-wide field imaging provides reliable color fundus capturing for the primary diagnosis of LD and may also be used as a screening tool. Wide-field imaging can be used for targeted documentation of LD lesions using true colors and with minimal optical distortions. Information on the status of the vitreoretinal interface, including detection of retinal holes, detachments, and vitreous tractions, can be obtained with peripheral structural optical coherence tomography (OCT) or scanning laser ophthalmoscopy in retro-mode. These techniques clarify the associated risks of rhegmatogenous retinal detachment. Fundus autofluorescence can provide details on atrophic changes. However, the risk of retinal detachment by means of this technique requires further investigation. OCT angiography may be successfully performed for some lesions. Taken together, OCT and OCT angiography demonstrate thinning of the choroid, alteration of local choroidal microcirculation, and, in severe lesions, involvement of the sclera. OCT angiography confirms loss of retinal microcirculation within LD lesion, which was previously shown with fluorescein angiography. In conclusion, despite relatively simple primary diagnosis, imaging of LD lesions remains challenging due to their peripheral localization. However, several new strategies, including ultra-wide field imaging, peripheral OCT, and scanning laser ophthalmoscopy, make LD imaging possible on a routine basis, improving diagnosis and understanding of LD pathogenesis.
PubMed: 37605766
DOI: 10.2147/OPTH.S405200 -
Progress in Retinal and Eye Research Nov 2023Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with... (Review)
Review
Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-β pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.
Topics: Humans; Retinal Detachment; Visual Acuity; Genetic Association Studies
PubMed: 36621380
DOI: 10.1016/j.preteyeres.2022.101158 -
International Journal of Molecular... Oct 2023The microtubule-associated protein tau is an intrinsically disordered protein containing a few short and transient secondary structures. Tau physiologically associates... (Review)
Review
The microtubule-associated protein tau is an intrinsically disordered protein containing a few short and transient secondary structures. Tau physiologically associates with microtubules (MTs) for its stabilization and detaches from MTs to regulate its dynamics. Under pathological conditions, tau is abnormally modified, detaches from MTs, and forms protein aggregates in neuronal and glial cells. Tau protein aggregates can be found in a number of devastating neurodegenerative diseases known as "tauopathies", such as Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), etc. However, it is still unclear how the tau protein is compacted into ordered protein aggregates, and the toxicity of the aggregates is still debated. Fortunately, there has been considerable progress in the study of tau in recent years, particularly in the understanding of the intercellular transmission of pathological tau species, the structure of tau aggregates, and the conformational change events in the tau polymerization process. In this review, we summarize the concepts of tau protein aggregation and discuss the views on tau protein transmission and toxicity.
Topics: Humans; tau Proteins; Protein Aggregates; Comprehension; Tauopathies; Alzheimer Disease
PubMed: 37834471
DOI: 10.3390/ijms241915023 -
Journal of Korean Medical Science May 2024The process of cancer metastasis is dependent on the cancer cells' capacity to detach from the primary tumor, endure in a suspended state, and establish colonies in... (Review)
Review
The process of cancer metastasis is dependent on the cancer cells' capacity to detach from the primary tumor, endure in a suspended state, and establish colonies in other locations. Anchorage dependence, which refers to the cells' reliance on attachment to the extracellular matrix (ECM), is a critical determinant of cellular shape, dynamics, behavior, and, ultimately, cell fate in nonmalignant and cancer cells. Anchorage-independent growth is a characteristic feature of cells resistant to anoikis, a programmed cell death process triggered by detachment from the ECM. This ability to grow and survive without attachment to a substrate is a crucial stage in the progression of metastasis. The recently discovered phenomenon named "adherent-to-suspension transition (AST)" alters the requirement for anchoring and enhances survival in a suspended state. AST is controlled by four transcription factors (IKAROS family zinc finger 1, nuclear factor erythroid 2, BTG anti-proliferation factor 2, and interferon regulatory factor 8) and can detach cells without undergoing the typical epithelial-mesenchymal transition. Notably, AST factors are highly expressed in circulating tumor cells compared to their attached counterparts, indicating their crucial role in the spread of cancer. Crucially, the suppression of AST substantially reduces metastasis while sparing primary tumors. These findings open up possibilities for developing targeted therapies that inhibit metastasis and emphasize the importance of AST, leading to a fundamental change in our comprehension of how cancer spreads.
Topics: Humans; Neoplasm Metastasis; Neoplasms; Cell Adhesion; Extracellular Matrix; Epithelial-Mesenchymal Transition; Anoikis; Transcription Factors
PubMed: 38769921
DOI: 10.3346/jkms.2024.39.e156 -
Science Advances Sep 2023Previous studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to...
Previous studies have revealed a role for proline metabolism in supporting cancer development and metastasis. In this study, we show that many cancer cells respond to loss of attachment by accumulating and secreting proline. Detached cells display reduced proliferation accompanied by a general decrease in overall protein production and de novo amino acid synthesis compared to attached cells. However, proline synthesis was maintained under detached conditions. Furthermore, while overall proline incorporation into proteins was lower in detached cells compared to other amino acids, there was an increased production of the proline-rich protein collagen. The increased excretion of proline from detached cells was also shown to be used by macrophages, an abundant and important component of the tumor microenvironment. Our study suggests that detachment induced accumulation and secretion of proline may contribute to tumor progression by supporting increased production of extracellular matrix and providing proline to surrounding stromal cells.
Topics: Proline; Amino Acids; Biological Transport; Extracellular Matrix; Macrophages; Neoplasms
PubMed: 37672588
DOI: 10.1126/sciadv.adh2023 -
The Journal of Clinical Investigation Dec 2023Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of...
Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.
Topics: Animals; Mice; Capillaries; Hypertriglyceridemia; Lipoprotein Lipase; Receptors, Lipoprotein; Triglycerides; Apolipoprotein A-V
PubMed: 37824203
DOI: 10.1172/JCI172600 -
Research Square Apr 2024To assess clinical factors leading to recurrent retinal detachment (RD) and characteristics of recurrence in patients with Stickler Syndrome.
OBJECTIVE
To assess clinical factors leading to recurrent retinal detachment (RD) and characteristics of recurrence in patients with Stickler Syndrome.
METHODS
Retrospective case series study of patients with clinical diagnosis of Stickler Syndrome who underwent rhegmatogenous RD repair. Recurrent RD after initial surgery was categorized as "early" if the recurrence was within 1 year or "late" if greater than 1 year.
RESULTS
Thirty eyes from 22 patients underwent rhegmatogenous RD repair. For initial repair, 13 eyes underwent pars plana vitrectomy combined with scleral buckling (PPV/SB), 16 eyes underwent primary scleral buckling (SB), and 1 eye underwent pneumatic retinopexy (PnR). Recurrent RD occurred in 6 (46%) PPV/SB eyes (5 early and 1 late), 10 (63%) SB eyes (3 early and 7 late), and 0 (0%) PnR eyes (p = 0.61). PPV/SB was preferred for eyes presenting with total detachment (82%), giant retinal tears (100%), and proliferative vitreoretinopathy (PVR) (80%). For eyes with early recurrent RD, 6 (75%) developed PVR leading to recurrence. For eyes with late recurrent RD, 7 (87.5%) developed a new retinal break leading to recurrence, including 4 with a break posterior to the buckle indentation apex. At last follow-up, median LogMAR visual acuity was 0.68 for eyes with recurrent RD compared to 0.29 for eyes without recurrence (p = 0.27).
CONCLUSIONS
Early recurrent RD was mostly caused by PVR, while late recurrent RD was mostly due to new retinal breaks. Eyes with seemingly uncomplicated rhegmatogenous RD repair with primary SB remained at high risk for late re-detachment.
PubMed: 38645110
DOI: 10.21203/rs.3.rs-3941698/v1