Tendon is a simple aligned fibre composite, consisting of collagen-rich fascicles surrounded by a softer interfascicular matrix (IFM). The composition and interactions between these material phases are fundamental in ensuring tissue mechanics meet functional requirements. However the IFM is poorly defined, therefore tendon structure-function relationships are incompletely understood. We hypothesised that the IFM has a more complex proteome, with faster turnover than the fascicular matrix (FM). Using laser-capture microdissection and mass spectrometry, we demonstrate that the IFM contains more proteins, and that many proteins show differential abundance between matrix phases. The IFM contained more protein fragments (neopeptides), indicating greater matrix degradation in this compartment, which may act to maintain healthy tendon structure. Protein abundance did not alter with ageing, but neopeptide numbers decreased in the aged IFM, indicating decreased turnover which may contribute to age-related tendon injury. These data provide important insights into how differences in tendon composition and turnover contribute to tendon structure-function relationships and the effects of ageing.
Summary This report describes four cases of intraocular melanoma which were treated with a course of human tyrosine DNA canine melanoma vaccine. Two cases continued to show progression of the tumour. One case presented with bilateral intraocular melanomas and demonstrated clinical progression in one eye within 5 months, and apparent quiescence of disease in the other, though subtle deterioration was noted at a 2‐year follow‐up. The final case presented with recurrent ulceration due to an intraocular melanoma and demonstrated a good clinical response with a reduction in the frequency and severity of the episodes of ulceration. The small number of cases in this report precludes firm conclusions, but these reported outcomes suggest limited justification for the routine recommendation of melanoma vaccines to horses with intraocular melanomas.
Introduction Our previous work indicates that the interfascicular matrix (IFM) is critical for tendon function, facilitating sliding between fascicles to allow the tendon to stretch and recoil [Thorpe, 2012]. This is particularly important in energy storing tendons such as the human Achilles tendon and equine superficial digital flexor tendon (SDFT), which experience strains as high as 16% during exercise [Stephens, 1989], and therefore require the capacity for considerable inter-fascicular sliding. However, the composition of the IFM is poorly characterised, and little is known about which proteins within the IFM enable this sliding behaviour. Therefore, the aim of this study was isolate, characterise and compare the proteome of the IFM and fascicular matrix (FM) in the equine SDFT. We hypothesised that the proteomic profile would differ between the FM and the IFM, with greater complexity and turnover in the IFM. Methods Sections from the mid-metacarpal region of grossly normal SDFTs (n = 10) were embedded in OCT and snap-frozen. Laser capture microdissection was used to isolate regions of the FM and IFM (Figure 1) from transverse cryosections. Abstract 104 Figure 1 Transverse section of the SDFT, showing appearance of the IFM (a). The IFM and FM were isolated using laser capture microdissection (b) Following protein solubilisation and tryptic digestion, peptides were identified using liquid chromatography mass spectrometry (LC-MS/MS), using an Ultimate 3000 Nano system (Dionex/Thermo Fisher Scientific) on line to a Q Exactive Quadrupole-Orbitrap instrument (Thermo- Fisher Scientific). Proteins within the IFM and FM were identified using Peaks® 7 Spider software, searching against the UniHorse database, with a false discovery rate (FDR) of 1%, a minimum of 2 peptides per protein and a confidence score > 50. Progenesis™ software was used to identify fold changes in protein abundance between the FM and IFM. Greater than 2 fold changes with FDR adjusted p values < 0.05 were considered to be significant. In addition, cleavage of matrix components was assessed by identification of non-tryptic peptides (neopeptides) in the FM and IFM. Results A total of 246 proteins were identified in the IFM, and 141 in the FM (significance score >50). 60 proteins showed a > 2 fold change between the FM and IFM. Of these, 48 proteins were enriched in the IFM, including collagen type III, histones and ribosomal proteins. 12 proteins were at lower abundance in the IFM, including type I collagen, thrombospondin-1 and 4, cartilage oligomeric matrix protein (COMP) and fibromodulin. Neopeptides for collagens type I, III, V, XI, COMP and decorin were identified in both FM and IFM samples. A greater number of collagen neopeptides were identified in the IFM than in the FM. Discussion This is the first work to provide a comprehensive analysis of proteins present within different regions of tendon. The data support our hypothesis, demonstrating a greater number of proteins within the IFM, and different levels of a large number of pro...
SummaryBackgroundFew reports describe the aetiology, presentation and diagnosis of retinal detachment in horses. Equine recurrent uveitis (ERU) and trauma are the most common causes of equine retinal detachment in the United States, but no studies have characterised the disease within the United Kingdom.ObjectivesTo describe clinical presentation, aetiology and diagnostic examination findings of horses with retinal detachment within a UK‐based population.Study designRetrospective case series.MethodsMedical records of horses presented to a single UK referral centre between 2010 and 2020 were reviewed. Horses were diagnosed with retinal detachment by clinical examination and/or ultrasonography, and details of clinical presentation, aetiology and examination findings were recorded.ResultsA total of 23 horses were included. There were 13 geldings and 10 mares with a median age of 9 at presentation (range 4 days to 17 years). Warmbloods were the most common breed (n = 8). Unilateral cases (n = 21) were more common than bilateral (n = 2). ERU was the most common aetiology (n = 10) followed by trauma (n = 8). Three cases presented post‐intraocular surgery, one congenital and one secondary to primary glaucoma. Ultrasound confirmed diagnosis in 23 (100%) cases, but only nine could be visualised by direct ophthalmoscopy. Cataracts, posterior synechiae and vitreal debris were found commonly in both the ipsilateral and contralateral eye affected.Main limitationsSmall sample size. Single‐centre retrospective study which may not be representative of the entire UK population. Histological confirmation of cases was not obtained.ConclusionsCauses of retinal detachment in the studied population are like those previously reported in the USA and most cases presented with complete detachment. Ocular ultrasound is useful in the diagnosis of retinal detachment when the fundus cannot be directly assessed. The presence of retinal detachment should be considered in non‐visual eyes presenting with cataracts, vitreal debris and posterior synechiae.
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