Developing novel anti-fibrotic therapeutics to modulate post-surgical wound healing in Glaucoma: big potential for small molecules

Ocular fibrosis leads to significant visual impairment and blindness in millions of people worldwide, and is one of the largest areas of unmet need in clinical ophthalmology. The antimetabolites, mitomycin C and 5-fluorouracil, are the current gold standards used primarily to prevent fibrosis after glaucoma surgery, but have potentially blinding complications like tissue damage, breakdown, and infection. This review thus focuses on the development of new classes of small molecule therapeutics to prevent post-surgical fibrosis in the eye, especially in the context of glaucoma filtration surgery. We discuss recent advances and innovations in ophthalmic wound healing research, including antibodies, RNA interference, gene therapy, nanoparticles, liposomes, dendrimers, proteoglycans, and small molecule inhibitors. We also review the challenges involved in terms of drug delivery, duration of action, and potential toxicity of new anti-fibrotic agents in the eye

Personalized Medicine in Ocular Fibrosis: Myth or Future Biomarkers

SIGNIFICANCE: Fibrosis-related events play a part in the pathogenesis or failure of treatment of virtually all the blinding diseases around the world, and also account for over 40% of all deaths. It is well established that the eye and other tissues of some group of patients, for example Afro-Caribbean people, scar worse than others. However, there is a current lack of reliable biomarkers to stratify the risk of scarring and postsurgical fibrosis in the eye. RECENT ADVANCES: Recent studies using genomics, proteomics, metabolomics, clinical phenotyping, and high-resolution in vivo imaging techniques have revealed potential novel biomarkers to identify and stratify patients at risk of scarring in different fibrotic eye diseases. CRITICAL ISSUES: Most of the studies, to date, have been done in animals or small cohorts of patients and future research is needed to validate these results in large longitudinal human studies. Detailed clinical phenotyping and effective biobanking of patient tissues will also be critical for future biomarker research in ocular fibrosis. FUTURE DIRECTIONS: The ability to predict the risk of scarring and to tailor the antifibrotic treatment regimen to each individual patient will be an extremely useful tool clinically to prevent undertreating, or exposing patients to unnecessary treatments with potential side effects. An exciting future prospect will be to use new advances in genotyping, namely next-generation whole genome sequencing like RNA-Seq, to develop a customized gene chip in ocular fibrosis. Successful translation of future biomarkers to benefit patient care will also ultimately require a strong collaboration between academics, pharmaceutical, and biotech companies

To live is better than to die = 好死不如賴活著

Film Director: Chen Weijun (陳為軍) Film Release Year: 2003https://commons.ln.edu.hk/ccs_worksheet/1005/thumbnail.jp

Leber hereditary optic neuropathy – Therapeutic challenges and early promise

AbstractLeber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder in the general population. It is an important cause of severe, usually irreversible, visual loss among young adults with a peak age of onset in the second and third decades of life. Management is currently mostly supportive but recent developments in LHON research are pointing the way towards more effective treatments for this blinding mitochondrial disorder

Some Examples of Family Floer Mirrors

In this article, we give explicit calculations for the family Floer mirrors of some non-compact Calabi-Yau surfaces. We compare it with the mirror construction of Gross-Hacking-Keel for suitably chosen log Calabi-Yau pairs and the rank two cluster varieties of finite type. In particular, the analytifications of the later two give partial compactifications of the family Floer mirrors that we computed.Comment: 38 pages, 15 figures, comments are welcom

The clinical manifestations and molecular mechanisms of mitrochondrial neuro-opthalmological disorders

Autosomal dominant optic atrophy (DOA) classically presents with bilateral, symmetric visual failure in early childhood, with the pathological hallmark being the selective loss of retinal ganglion cells (RGCs). In the first population-based epidemiological study of DOA, we were able to estimate its minimum prevalence at 1 in 35,000 in the North of England. In independent case series from Northern Europe and North America, the majority of families with DOA harboured pathogenic OPA1 mutations (50.0-57.6%), and large-scale OPA1 rearrangements were present in only a small subgroup (11.1-12.9%). We also confirmed that OPA3 mutations were very rare in non-syndromal DOA cases. Visual deterioration was observed in over half (54.2-67.4%) of all patients during long term follow-up, and the rate of visual decline varied markedly both between and within families. In a large multi-centre study of 104 OPA1-positive patients from 45 independent families, we established that additional neuromuscular complications are common in OPA1 disease, affecting up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and chronic progressive external ophthalmoplegia (CPEO) from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. Patients with these syndromal disease variants (DOA+) had a worse visual prognosis, and this was associated with a more pronounced reduction in retinal nerve fibre layer thickness compared to patients with pure DOA. Interestingly, there was a two- to three-fold increased risk of developing DOA+ features with missense OPA1 mutations and those located within the GTPase domain.EThOS - Electronic Theses Online ServiceMedical Research Council (UK)GBUnited Kingdo

Clinical utility gene card for : inherited optic neuropathies including next-generation sequencing-based approaches

Non peer reviewe

The missing group? Situating transnational contacts in defamilisation research

Defamilisation research is increasingly seen as an important component of studies of welfare and social work. It is concerned with people’s vulnerability to defamilisation risks, which are caused by insufficient opportunities for people to choose whether and how they participate in the family. Despite an increasing emphasis on defamilisation research, there has been insufficient attention given to how studies of transnational contacts contribute to defamilisation research. This article argues for the need to expand the scope of defamilisation research to incorporate the concept of ‘transnational contact-led strategies’ using evidence from focus groups with Chinese older people in the United Kingdom

Disorders of the Optic Nerve in Mitochondrial Cytopathies: New Ideas on Pathogenesis and Therapeutic Targets

Mitochondrial cytopathies are a heterogeneous group of human disorders triggered by disturbed mitochondrial function. This can be due to primary mitochondrial DNA mutations or nuclear defects affecting key components of the mitochondrial machinery. Optic neuropathy is a frequent disease manifestation and the degree of visual failure can be profound, with a severe impact on the patient’s quality of life. This review focuses on the major mitochondrial disorders exhibiting optic nerve involvement, either as the defining clinical feature or as an additional component of a more extensive phenotype. Over the past decade, significant progress has been achieved in our basic understanding of Leber hereditary optic neuropathy and autosomal-dominant optic atrophy—the two classical paradigms for these mitochondrial optic neuropathies. There are currently limited treatments for these blinding ocular disorders and, ultimately, the aim is to translate these major advances into tangible benefits for patients and their families