THE EFFECT OF INTERNAL LIMITING MEMBRANE PEELING ON THE INNER RETINAL LAYERS IN PATIENTS WITHOUT MACULAR PATHOLOGIC CONDITION.

BACKGROUND: To examine the effect of internal limiting membrane peeling on the inner retinal layers in patients without macular pathological condition. METHODS: A prospective nonrandomized trial of patients undergoing pars plana vitrectomy with internal limiting membrane peeling for pathologic condition outside the macula was performed. Optical coherence tomography including macular ganglion cell layer, inner plexiform layer, and peripapillary retinal nerve fiber layer imaging was performed before surgery, 1, 3, and 6 months postoperatively, and at the end of follow-up (ranges between 4 and 17 months). Patients with any macular pathological condition on optical coherence tomography before surgery were excluded. The main outcome measure was change in thickness of the ganglion cell layer and inner plexiform layer. RESULTS: Ten patients who underwent pars plana vitrectomy with internal limiting membrane peeling for macula-on retinal detachment were included in the analysis. The mean age was 55 years, and the mean follow up was 10.8 months. All patients completed at least two postoperative follow-up visits that included an optical coherence tomography as per the protocol (range 2-6 months). There was an immediate reduction in the global (G), inferotemporal, superotemporal, and superior (S) ganglion cell layer thickness at the first follow up as compared with the preoperative state ( P = 0.028, P = 0.027, P = 0.026, and P = 0.027 respectively). From the first follow-up visit onward until the final follow-up, the thinning persisted, although there was no further statistically significant thinning. CONCLUSION: Peeling of the internal limiting membrane causes significant ganglion cell layer thinning in maculae without pathologic condition before surgery. At up to 17 months of follow-up, this effect seems to be immediate and nonprogressive.

The protease inhibitor E64d might attenuate the development of experimental anti-glomerular basement membrane disease through regulating the activation of Th1 cells.

BACKGROUND: Cathepsins have been recently identified as a regulator in the activation of Th1 and Th17 cells, which play an important role in the pathogenesis of anti-glomerular basement membrane (GBM) disease. Whether cathepsins contribute to the development of anti-GBM disease through regulating the activation of CD4+ T cell is still unclear. METHODS: Rats with experimental anti-GBM disease was established by immunization with the nephritogenic T cell epitope α3127-148. E64d, a cysteine cathepsin inhibitor, was administered in vitro and vivo to evaluate the effect of cathepsins on regulating the activation of antigen specific T cells and the development of anti-GBM disease. RESULTS: In rats with experimental anti-GBM diseases, E64d treatment not only reduced the levels of proteinuria, serum creatinine and anti-GBM antibody, but also ameliorated the kidney injury with less glomerular IgG deposition, a lower percentage of crescents and less infiltration of CD4+ T cells, CD8+ T cells and macrophages, as well as a lower percentage of splenic Th1 cells. In vitro, E64d treatment could significantly reduce the production of IFN-γ in the supernatant which might be produced by the activation of Th1 cells after being recalled with the autoantigen α3127-148. We also found the CD4+ T cells of rats with anti-GBM disease had an increased expression of cathepsin L (Cts-L), and the percentage of CD4+ T cells with extracellular expression of Cts-L was obviously higher, indicating it as a potential key regulator. CONCLUSIONS: E64d might attenuate the development of anti-GBM disease by participating in the activation of Th1 cells, indicating it as a potential drug for anti-GBM disease in the future.

Recurrent atypical antiglomerular basement membrane nephritis in the kidney transplant.

Atypical antiglomerular basement membrane (anti-GBM) nephritis can be defined as linear GBM staining for monotypic or polytypic immunoglobulin (Ig) by immunofluorescence (IF) without a diffuse crescentic pattern. We describe the clinicopathologic features of 6 patients (18 biopsies) in this first series of recurrent atypical anti-GBM nephritis after kidney transplantation. Recurrent glomerulonephritis occurred at a mean of 3.8 months posttransplant (range 1-7 months). Three index biopsies were for clinical indication, and 3 were protocol biopsies. Glomerular histologic changes were mild, with 2 showing segmental endocapillary hypercellularity, 1 focal glomerular microangiopathy, and the others no significant glomerular histologic changes. All 6 allografts showed monotypic linear glomerular Ig staining by IF: IgG kappa (n = 2), IgG lambda, IgA kappa, IgA lambda, and IgM lambda. Follow-up biopsies were available for 5 patients and showed similar histologic and IF findings without evidence of significant progression. No patients had detectable serum anti-GBM antibody or monoclonal proteins. The mean serum creatinine level on follow-up (24-62 months posttransplant) was 1.8 (range 0.93-2.77) mg/dL; no grafts were lost to recurrent disease. This series demonstrates that monotypic atypical anti-GBM recurs in the allograft and supports the idea that this disease is due to a circulating monoclonal protein.

Breaking through the basement membrane barrier to improve nanotherapeutic delivery to tumours.

An effective nanotherapeutic transport from the vasculature to the tumour is crucial for cancer treatment with minimal side effects. Here we demonstrate that, in addition to the endothelial barrier, the tumour vascular basement membrane surrounding the endothelium acts as a formidable mechanical barrier that entraps nanoparticles (NPs) in the subendothelial void, forming perivascular NP pools. Breaking through this basement membrane barrier substantially increases NP extravasation. Using inflammation triggered by local hyperthermia, we develop a cooperative immunodriven strategy to overcome the basement membrane barrier that leads to robust tumour killing. Hyperthermia-triggered accumulation and inflammation of platelets attract neutrophils to the NP pools. The subsequent movement of neutrophils through the basement membrane can release the NPs entrapped in the subendothelial void, resulting in increased NP penetration into deeper tumours. We show the necessity of considering the tumour vascular basement membrane barrier when delivering nanotherapeutics. Understanding this barrier will contribute to developing more effective antitumour therapies.

The Immunobiological Agents for Treatment of Antiglomerular Basement Membrane Disease.

Combination therapy with glucocorticoids, cyclophosphamide, and plasmapheresis is recommended as the standard treatment for anti-glomerular basement membrane (anti-GBM) disease, but the prognosis of this disease remains poor. Several immunobiological agents have been administered or are expected to be useful for anti-GBM disease in light of refractory disease or the standard treatments' tolerability. Many data regarding the use of biologic agents for anti-GBM disease have accumulated, verifying the effectiveness and potential of biologic agents as a new treatment option for anti-GBM disease. Tumor necrosis factor (TNF) inhibitors were shown to be useful in animal studies, but these agents have no clinical use and were even shown to induce anti-GBM disease in several cases. Although the efficacy of the TNF-receptor antagonist has been observed in animal models, there are no published case reports of its clinical use. There are also no published reports of animal or clinical studies of anti-B-cell-activating factor, which is a member of the TNF family of agents. Anti-interleukin (IL)-6 antibodies have been demonstrated to have no effect on or to exacerbate nephritis in animal models. Anti-C5 inhibitor was observed to be useful in a few anti-GBM disease cases. Among the several immunobiological agents, only rituximab has been demonstrated to be useful in refractory or poor-tolerance patients or small uncontrolled studies. Rituximab is usually used in combination with steroids and plasma exchange and is used primarily as an alternative to cyclophosphamide, but there is insufficient evidence regarding the efficacy of rituximab for anti-GBM disease, and thus, randomized controlled studies are required.

360-degree pedicled inverted internal limiting membrane flap technique without face-down posturing for large idiopathic macular holes: a retrospective case series.

PURPOSE: This study aimed to determine closure rates of large idiopathic macular holes treated with pars plana vitrectomy and 360-degree pedicled inverted internal limiting membrane flap without face-down posturing and define visual improvement, types of macular hole closure, and external retina integrity as secondary outcomes. METHODS: This retrospective case series analyzed all patients who were treated by vitrectomy, 360-degree pedicled inverted internal limiting membrane flap, and gas tamponade, without face-down posturing postoperatively. Age, sex, time of visual acuity reduction, other ocular pathologies, and lens status were collected. The best-corrected visual acuity and optical coherence tomography results were recorded during pre- and postoperative follow-up examinations (15 days and 2 months after surgery). RESULTS: This study enrolled 20 eyes of 19 patients, and the mean age was 66 years. Optical coherence tomography performed 2 months after surgery revealed hole closure in 19 (95%) eyes. The median best-corrected visual acuity improved from +1.08 preoperatively to +0.66 LogMAR 2 months postoperatively (p<0.001), with a median of 20 letters of visual improvement (0.4 LogMAR) on the Early Treatment Diabetic Retinopathy Study chart. V (47.36%)- and U (52.63%)-types of closure were observed. CONCLUSION: The 360-degree pedicled inverted internal limiting membrane flap technique, without face-down posturing, provided a high closure rate (95%), external layer recovery, and V- and U-type foveal closure contours, in addition to visual improvement in most cases of large macular holes (even macular holes >650 µm). This technique may be a viable alternative to patients in whom traditional postoperative face-down positioning for large macular hole treatment is not possible.

A Hematopoietic Stem Cell Transplant Recipient with Nephrotic Syndrome and Immune Complex Deposits in Tubular Basement Membrane: A Rare Case Report.

Following allogenic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) may develop which may affect several organs. Although the presence of nephrotic syndrome after HSCT is rare, sometimes it occurs in the setting of GVHD. The most common histological finding on kidney biopsy of patients with proteinuria owing to GVHD is membranous glomerulonephritis (MGN). However, reports of immune complex deposition in the tubular basement membrane (TBM) and glomerular basement membrane (GBM) are extremely rare. Herein we present a 65-year-old female with a history of HSCT at six years ago who was referred to Dr.Shariati Hospital in Tehran with nephrotic syndrome. Secondary serologic laboratory tests were all normal. The histopathologic study indicated diffuse GBM and TBM thickening, spike formation, infiltration of inflammatory mononuclear cells in tubulointerstitial area and acute tubular injury in light microscopy. Immunofluorescence staining showed immune complex deposits in GBM, mesangial cells, and TBM.  DOI: 10.52547/ijkd.7550.

A case report and literature study on Alport syndrome featuring nephrotic syndrome as its primary manifestation.

BACKGROUND: Historically, due to the lack of distinct clinical symptoms, Alport syndrome, a hereditary kidney disease prevalent in children and a leading cause of kidney failure, has often been misdiagnosed as other kidney conditions. CASE DESCRIPTION: This article presents a comprehensive review and analysis of clinical data concerning a child diagnosed with Alport syndrome, where nephrotic syndrome served as the primary manifestation. The male child in this case exhibited symptoms starting at the age of 6, initially diagnosed as nephrotic syndrome. Consequently, oral steroid medication was administered, proving ineffective. Due to persistent proteinuria and microscopic hematuria, a renal biopsy was performed. Immunofluorescence staining revealed no abnormal expression of the α3, α4, and α5 chains of type IV collagen. Notably, electron microscopy revealed the basement membrane to be partially torn and arachnoid. Genetic testing indicated a hemizygous COL4A5 acceptor-splice-site mutation c.4707-1(IVS50)G > A, inherited from his mother. CONCLUSION: This specific mutated locus, being the first of its kind reported, adds valuable information to the existing gene mutation spectrum of Alport syndrome. Consequently, it emphasizes the importance for clinicians to deepen their understanding of rare kidney diseases, contributing to enhanced diagnostic accuracy and improved patient care.

The Role of MMP-9 in Regulating Degradation of the Splenic Microvascular Basement Membrane Induced by High Altitude Hypoxia / Rol de la MMP-9 en la Regulación de la Degradación de la Membrana Basal Microvascular Esplénica Inducida por Hipoxia de Altura

SUMMARY: To investigate changes of MMP-9 in the rat spleen and hypoxia-induced microvascular basement membrane under high altitude hypoxia. Thirty male specific pathogen-free Sprague Dawley rats were randomly divided into control and hypoxia groups, with 15 rats in each group. The rats in the control group were placed in Dingxi City, Gansu Province (2080 m above sea level) for 30 days. Rats in the hypoxia group were raised in a hypoxic environment in Maduo County, Qinghai Province (4300 m above sea level), for 30 days to establish a hypoxic rat model. Routine blood tests, MMP-9 mRNA, MMP-9 protein, and the spleen microvascular basement membrane were detected. (1) Compared with the control group, the red blood cell count, hemoglobin, and hematocrit levels of the rats in the hypoxia group were all increased; thus, a hypoxia model was successfully established. (2) Compared with the control group, the expression of MMP-9 mRNA and protein was significantly higher in the spleen of rats in the hypoxic group, and the difference was statistically significant (P <0.05). (3) Compared with the control group, the blood vessel basement membrane in the spleen of the hypoxia group was degraded. Under natural low air pressure and high altitude conditions, the expression of MMP-9 in rat spleen tissue increases and participates in the degradation of the microvascular basement membrane.

El objetivo de este trabajo fue investigar los cambios de la MMP-9 en el bazo de la rata y la membrana basal microvascular inducida bajo hipoxia a gran altura. Treinta ratas macho Sprague Dawley, libres de patógenos específicos, se dividieron aleatoriamente en dos grupos de 15 ratas cada uno, un grupo control y un grupo hipoxia. Durante 30 días las ratas del grupo control estuvieron en la ciudad de Dingxi, provincia de Gansu (2080 m sobre el nivel del mar). Las ratas del grupo de hipoxia se criaron en un entorno hipóxico en el condado de Maduo, provincia de Qinghai (4300 m sobre el nivel del mar), durante 30 días para establecer un modelo de rata hipóxica. Se realizaron análisis de sangre de rutina, ARNm de MMP-9, proteína MMP-9 y de la membrana basal microvascular del bazo. En comparación con el grupo control, el recuento de glóbulos rojos, la hemoglobina y los niveles de hematocrito de las ratas del grupo de hipoxia aumentaron; por lo tanto, se estableció con éxito un modelo de hipoxia. En comparación con el grupo control, la expresión de ARNm y proteína de MMP-9 fue significativamente mayor en el bazo de las ratas del grupo hipóxico, siendo la diferencia estadísticamente significativa (P <0,05). En comparación con el grupo control, la membrana basal de los vasos sanguíneos estaba degradada en el bazo del grupo hipoxia. En condiciones naturales de baja presión atmosférica y gran altitud, la expresión de MMP-9 en el tejido del bazo de la rata aumenta y participa en la degradación de la membrana basal microvascular.

Screening of hub inflammatory bowel disease biomarkers and identification of immune-related functions based on basement membrane genes.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, inflammatory, and autoimmune disease, but its specific etiology and pathogenesis are still unclear. This study aimed to better discover the causative basement membrane (BM) genes of their subtypes and their associations. METHODS: The differential expression of BM genes between CD and UC was analyzed and validated by downloading relevant datasets from the GEO database. We divided the samples into 3 groups for comparative analysis. Construction of PPI networks, enrichment of differential gene functions, screening of Lasso regression models, validation of ROC curves, nomogram for disease prediction and other analytical methods were used. The immune cell infiltration was further explored by ssGSEA analysis, the immune correlates of hub BM genes were found, and finally, the hub central genes were screened by machine learning. RESULTS: We obtained 6 candidate hub BM genes related to cellular immune infiltration in the CD and UC groups, respectively, and further screened the central hub genes ADAMTS17 and ADAMTS9 through machine learning. And in the ROC curve models, AUC > 0.7, indicating that this characteristic gene has a more accurate predictive effect on IBD. We also found that the pathogenicity-related BM genes of the CD and UC groups were mainly concentrated in the ADAMTS family (ADAMTS17 and ADAMTS9). Addition there are some differences between the two subtypes, and the central different hub BM genes are SPARC, POSTN, and ADAMTS2. CONCLUSIONS: In the current study, we provided a nomogram model of CD and UC composed of BM genes, identified central hub genes, and clarified the similarities and differences between CD and UC. This will have potential value for preclinical, clinical, and translational guidance and differential research in IBD.

Baseline reticular basement membrane morphology is related to subsequent spirometry deterioration in pediatric chronic airway inflammation: a follow-up study.

Reticular basement membrane (RBM) thickening may occur in children with allergic bronchial asthma (BA), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD). Its functional consequences remain unknown. We investigated the relationship between baseline RBM thickness and subsequent spirometry. In our cohort follow-up study, patients aged 3-18 yr with BA, CF, and PCD and controls underwent baseline lung clearance index (LCI) measurement, spirometry, and endobronchial biopsy sampling. Total RBM and collagen IV-positive layer thickness were measured. Trends in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), and FEV1/FVC were analyzed during follow-up, and their relationship to baseline characteristics was studied using univariate analysis and multiple regression models. Complete baseline data were available in 19 patients with BA, 30 patients with CF, 25 patients with PCD, and 19 controls. The RBM was thicker in patients with BA (6.33 ± 1.22 µm), CF (5.60 ± 1.39 µm), and PCD (6.50 ± 1.87 µm) than in controls (3.29 ± 0.55 µm) (all P < 0.001). The LCI was higher in patients with CF (15.32 ± 4.58, P < 0.001) and PCD (10.97 ± 2.46, P = 0.002) than in controls (7.44 ± 0.43). The median follow-up times were 3.6, 4.8, 5.7, and 1.9 years in patients with BA, CF, PCD, and controls, respectively. The z-scores of FEV1 and FEV1/FVC deteriorated significantly in all groups except in controls. In patients with CF and PCD, trends in FEV1 z-scores correlated with baseline LCI and RBM; in BA, it correlated with collagen IV. In multiple regression models, RBM morphology and ventilation inhomogeneity could predict up to 84.4% of variability in spirometry trends. In conclusion, baseline LCI value and RBM morphology may predict trends in subsequent spirometry.NEW & NOTEWORTHY This paper deals with the relationship between reticular basement membrane (RBM) morphology at baseline and follow-up spirometry in children with asthma, cystic fibrosis, and primary ciliary dyskinesia. For the first time, to our knowledge, the possibility to predict subsequent lung function development using selected baseline characteristics (reticular basement membrane morphology from endobronchial biopsy and ventilation inhomogeneity from nitrogen multiple breath washout test) is proposed. Corresponding predictive models are presented.

Basement membrane proteins in extracellular matrix characterize NF1 neurofibroma development and response to MEK inhibitor.

Neurofibromatosis type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of neurofibromas is an abundant collagen-rich extracellular matrix (ECM) that constitutes more than 50% of the tumor dry weight. However, little is known about the mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation of ECM enrichment during plexiform neurofibroma (pNF) development and identified basement membrane (BM) proteins, rather than major collagen isoforms, as the most upregulated ECM component. Following MEK inhibitor treatment, the ECM profile displayed an overall downregulation signature, suggesting ECM reduction as a therapeutic benefit of MEK inhibition. Through these proteomic studies, TGF-ß1 signaling was identified as playing a role in ECM dynamics. Indeed, TGF-ß1 overexpression promoted pNF progression in vivo. Furthermore, by integrating single-cell RNA sequencing, we found that immune cells including macrophages and T cells produce TGF-ß1 to induce Schwann cells to produce and deposit BM proteins for ECM remodeling. Following Nf1 loss, neoplastic Schwann cells further increased BM protein deposition in response to TGF-ß1. Our data delineate the regulation governing ECM dynamics in pNF and suggest that BM proteins could serve as biomarkers for disease diagnosis and treatment response.

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

In light chain amyloidosis (LA), the massive glomerular and vascular amyloid deposition leading to interstitial fibrosis/tubular atrophy (IFTA) is thought to be responsible for renal failure. The amyloid deposition in the interstitium and the tubular basement membrane (TBM) has received less attention in the study of LA. We, therefore, collected clinical and laboratory data on patients diagnosed with LA in our Nephrology Department and studied amyloid deposition in the TBM. Twelve LA patients were diagnosed by renal biopsy during a seven-year period. In 4 of the 12, amyloid deposition could also be detected in the TBM. In our first case of a patient with diabetes mellitus, non-amyloid fibrils resembling 'diabetic fibrillosis' were also seen by electron microscopy. Despite the double damage, IFTA was negligible, blood vessels were unaffected, and the glomerular deposition was segmental. In the other three cases, significant (>50%) IFTA and a severely reduced estimated glomerular filtration rate were already detected at the time of diagnosis and amyloid deposition was also observed in the blood vessels. These findings indicate the importance of TBM amyloid deposition in the progression of renal disease. This may represent a late-stage presentation of the disease with a heavy LC burden.

Basement membrane thickness helps to differentiate hypopigmented mycosis fungoides from clinical and pathological mimickers.

BACKGROUND: Hypopigmented mycosis fungoides (HMF) is a relatively rare subtype of mycosis fungoides (MF). The diagnosis of HMF can be quite challenging in case of insufficient diagnostic criteria due to the diverse conditions that present with hypopigmented lesions. This study aimed to evaluate the usefulness of the assessment of the basement membrane thickness (BMT) in the diagnosis of HMF. METHODS: A retrospective study was conducted on biopsy specimens of 21 HMF and 25 non-HMF cases who presented with hypopigmented lesions. The thickness of the basement membrane was evaluated in periodic acid-Schiff (PAS)-stained sections. RESULTS: The mean BMT was significantly higher in the HMF group than in the non-HMF group (P < 0.001). The best cut-off value of mean BMT for the detection of HMF verified in ROC analysis was 32.7 µm (P < 0.001) with a sensitivity of 85.7% and a specificity of 96%. CONCLUSION: Evaluation of BMT can be a useful tool to distinguish HMF from other causes of hypopigmented lesions in doubtful cases. We suggest the use of " BMT more than 33 µm" as a histopathologic criterion of HMF.

A randomised controlled trial evaluating internal limiting membrane peeling forceps in macular hole surgery.

PURPOSE: To assess study design and a range of anatomical and functional changes after internal limiting membrane (ILM) peeling using forceps developed for atraumatic ILM pick-up compared to standard forceps. METHODS: We conducted a masked proof-of concept randomised controlled trial (RCT) on 65 patients who underwent ILM peeling for idiopathic full-thickness macular hole (FTMH) using etched-tip forceps (etched-tip group, 33 eyes) compared to standard ILM forceps (smooth-tip group, 32 eyes). Patients were assessed preoperatively, 3 weeks, 3 and 6 months postoperatively. RESULTS: The primary closure rate was 95.4%. There was no statistically significant difference between the groups in terms of final visual acuity (66.9 vs 70.9 ETDRS letters, p = 0.13), difference of visual field mean deviation (1.32 vs 1.14 decibels), and number of eyes with pick-up-related retinal haemorrhages (16% vs 16%, p = 0.96), swelling of arcuate nerve fibre layer lesions (63% vs 55%, p = 0.54), number of dissociated optic nerve fibre layer lesions (31.4 vs 41.0, p = 0.16), nor inner retina defects (37% vs 22%, p = 0.17). Similar changes in inner retinal volumes were detected in all 9 sectors of an ETDRS grid except for a trend (p = 0.06) towards a lower reduction in the inferior inner sector in the etched-tip group. CONCLUSIONS: The study was successfully completed with masking maintained and a low risk of bias. Multiple endpoints relating to ILM peeling were assessed, and estimates were provided that can be used for future studies. Although the study was not powered to assess any specific endpoint, the anatomical and functional outcomes assessed did not significantly differ.

KCTD1 and Scalp-Ear-Nipple ('Finlay-Marks') syndrome may be associated with myopia and Thin basement membrane nephropathy through an effect on the collagen IV α3 and α4 chains.

INTRODUCTION: Scalp-Ear-Nipple syndrome is caused by pathogenic KCTD1 variants and characterised by a scalp defect, prominent ears, and rudimentary breasts. We describe here further clinical associations in the eye and kidney. METHODS: Fifteen affected members from two unrelated families with p.(Ala30Glu) or p.(Pro31Leu) in KCTD1 were examined for ocular and renal abnormalities. The relevant proteins were studied in the eye and kidney, and the mutation consequences determined from mouse knockout models. RESULTS: Five males and 10 females with a median age of 40 years (range 1-70) with pathogenic variants p.(Ala30Glu) (n = 12) or p.(Pro31Leu) (n = 3) in KCTD1 were studied. Of the 6 who underwent detailed ophthalmic examination, 5 (83%) had low myopic astigmatism, the mean spherical equivalent of 10 eyes was 2.38D, and one (17%) had hypermetropic astigmatism. One female had a divergent strabismus.Five individuals had renal cysts (5/15, 33%), with renal biopsy in one demonstrating a thinned glomerular basement membrane identical to that seen in Thin basement membrane nephropathy (AD Alport syndrome).In the eye, KCTD1 and its downstream targets, TFAP2, and the collagen IV α3 and α4 chains localised to the cornea and near the retinal amacrine cells. In the kidney, all these proteins except TFAP2 were expressed in the podocytes and distal tubules. TFAP2B and COL4A4 knockout mice also had kidney cysts, and COL4A3 and COL4A4 knockout mice had myopia. CONCLUSION: Individuals with a pathogenic KCTD1 variant may have low myopic astigmatism and represent a further rare genetic cause for a thinned glomerular basement membrane.

Large Internal Limiting Membrane Tears: Prevalence, Clinical Characteristics, and Surgical Utility.

PURPOSE: To describe the prevalence, clinical and imaging characteristics, and surgical utility of large internal limiting membrane (ILM) tears in eyes with epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. METHODS: This was a single-institution study including 71 eyes of 70 consecutive patients that underwent ERM peeling by a single vitreoretinal surgeon between 2016 and 2019. Demographic and clinical data were collected from the medical record. ERMs and large ILM tears were identified and analyzed on multimodal imaging. The main outcome measures were the prevalence and characteristics of large ILM tears in eyes undergoing ERM peeling. RESULTS: Large ILM tears were present in 23 of 71 eyes (32.4%) with ERM that underwent surgical management. A review of patients with ERM during the same period who did not undergo surgical management found large ILM tears in 8 of 100 eyes (8.0%). Large ILM tears were commonly associated with other signs of ERM-induced retinal traction, including retinal nerve fiber layer schisis in 20 of 23 eyes (87.0%), inner retinal dimpling in 8 of 23 eyes (34.8%), and discrete paravascular red lesions in 16 of 19 eyes (84.2%). In all eyes stained with brilliant blue G, the preoperative diagnosis of large ILM tear was confirmed and the scrolled ILM edge was used successfully to initiate ILM peeling. CONCLUSIONS: Large ILM tears are often present in eyes undergoing surgery for ERM and are likely caused by ERM contracture. Careful preoperative identification of these tears is helpful for surgical planning because the scrolled flap of ILM provides a convenient and safe "handle" for initiating membrane peeling.

Defining invasion in breast cancer: the role of basement membrane.

Basement membrane (BM) is an amorphous, sheet-like structure separating the epithelium from the stroma. BM is characterised by a complex structure comprising collagenous and non-collagenous proteoglycans and glycoproteins. In the breast, the thickness, density and composition of the BM around the ductal lobular system vary during differing development stages. In pathological conditions, the BM provides a physical barrier that separates proliferating intraductal epithelial cells from the surrounding stroma, and its absence or breach in malignant lesions is a hallmark of invasion and metastases. Currently, diagnostic services often use special stains and immunohistochemistry (IHC) to identify the BM in order to distinguish in situ from invasive lesions. However, distinguishing BM on stained sections, and differentiating the native BM from the reactive capsule or BM-like material surrounding some invasive malignant breast tumours is challenging. Although diagnostic use of the BM is being replaced by myoepithelial cell IHC markers, BM is considered by many to be a useful marker to distinguish in situ from invasive lesions in ambiguous cases. In this review, the structure, function and biological and clinical significance of the BM are discussed in relation to the various breast lesions with emphasis on how to distinguish the native BM from alternative pathological tissue mimicking its histology.

Anti-glomerular basement membrane glomerulonephritis concurrent with membranous nephropathy and acute tubular interstitial nephritis in a lung cancer patient treated with pembrolizumab.

Immune checkpoint inhibitors (ICIs) have become the standard treatment for many types of cancer and have improved patient prognosis. However, ICIs upregulate the immune system against tumors, leading to immune-related adverse events (irAEs). Kidney irAEs are less common, and most of them are acute tubulointerstitial nephritis (ATIN). However, there has been a recent increase in recognition of glomerular disease related to ICI therapies. We report the case of a 65-year-old man with lung adenocarcinoma who was treated with pembrolizumab (a monoclonal antibody targeting programmed cell death protein-1 [PD-1]). Pembrolizumab was discontinued after seven cycles due to the development of destructive thyroiditis. Within three months of discontinuing the pembrolizumab treatment, the patient developed rapid progressive glomerulonephritis (RPGN), liver dysfunction, and dysgeusia. The patient underwent renal biopsy and was diagnosed with crescentic glomerulonephritis due to anti-glomerular basement membrane (GBM) antibodies complicated with membranous nephropathy (MN) and ATIN. Treatment with systemic corticosteroids resulted in a favorable clinical response. Various ICI-associated glomerular diseases have been described; however, this is the first reported case of anti-GBM glomerulonephritis associated with MN and ATIN following ICI treatment.

Basement Membrane Changes of Myofiber and Fibrosis in Sternocleidomastoid Muscle of Congenital Muscular Torticollis.

OBJECTIVE: To investigate the correlation between the features of basement membranes (BMs) of residual myofibers in the sternocleidomastoid muscle (SCM) and fibrosis of congenital muscular torticollis (CMT) in children, and to evaluate the relationship between BM changes and appearance of CMT. MATERIALS AND METHODS: We reviewed the CMT patients from 2017 to 2018 and performed pathological studies. Forty resected specimens were stained by hematoxylin and eosin and Masson collagen staining. Immunohistochemical staining of collagen IV and laminin was also performed. Five adductor muscle specimens from patients with developmental dysplasia of the hip were used as the control group. RESULTS: Hematoxylin and eosin staining revealed apparent interstitial fibrosis around residual myofibers in lesion specimens. However, the severity of fibrosis differed within the same samples. The average percent area of fibrous tissue in affected SCMs and controls were different significantly. Immunohistochemical staining of collagen IV and laminin showed these proteins were mostly expressed in the BM and vascular wall of affected SCM. However, BMs and myofibers from three different areas within the same SCM tissue exhibited significant differences in proteins expression. CONCLUSIONS: Therefore, the defective BMs are associated with myofiber and mesenchyme fibrosis in patients with CMT, which is crucial for understanding the histopathology of SCM.