A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease

The effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans - A case study

Abstract Background A prospective analysis of the effect of autologous adipose derived mesenchymal stem cell (MSC) therapy in the treatment of an osteochondral defect of the knee with early progressive osteoarthritis following unsuccessful surgical intervention of osteochondritis dissecans (OCD). Case presentation After failed conventional management of OCD a patient undergoes intra-articular MSC therapy. Patient outcome measures included the Numeric Pain Rating Scale (NPRS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Structural outcome was assessed using MRI with the novel technique of T2 mapping used to indicate cartilage quality. Following MSC therapy the patient reported improvement in pain and function as measured by NPRS, WOMAC and KOOS. Repeat MRI analysis showed regeneration of cartilage. MRI T2 mapping indicated hyaline like cartilage regrowth. Conclusion In this report, the use of MSCs, after unsuccessful conventional OCD management, resulted in structural, functional and pain improvement. These results highlight the need to further study the regenerative potential of MSC therapy. Trial registration Australian and New Zealand Clinical Trial Registry Number - ACTRN12615000258550 (Date registered 19/03/2015 – retrospectively registered)

Mesenchymal stem cell therapy in the treatment of osteoarthritis:Reparative pathways, safety and efficacy - A review

Osteoarthritis is a leading cause of pain and disability across the world. With an aging population its prevalence is likely to further increase. Current accepted medical treatment strategies are aimed at symptom control rather than disease modification. Surgical options including joint replacement are not without possible significant complications. A growing interest in the area of regenerative medicine, led by an improved understanding of the role of mesenchymal stem cells in tissue homeostasis and repair, has seen recent focused efforts to explore the potential of stem cell therapies in the active management of symptomatic osteoarthritis. Encouragingly, results of pre-clinical and clinical trials have provided initial evidence of efficacy and indicated safety in the therapeutic use of mesenchymal stem cell therapies for the treatment of knee osteoarthritis. This paper explores the pathogenesis of osteoarthritis and how mesenchymal stem cells may play a role in future management strategies of this disabling condition

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease