Non-infectious uveitis (NIU) is an intractable, recurrent, and painful disease that is a common cause of vision loss. Available treatments of NIU, such as the use of topical corticosteroids, are non-specific and have serious side effects which limits them to short-term use; however, NIU requires long-term treatment to prevent vision loss. Therefore, a single dose therapeutic that mediates long-term immunosuppression with minimal side effects is desirable. In order to develop an effective long-term therapy for NIU, an adeno-associated virus (AAV) gene therapy approach was used to exploit a natural immune tolerance mechanism induced by the human leukocyte antigen G (HLA-G). To mimic the prevention of NIU, naïve Lewis rats received a single intravitreal injection of AAV particles harboring codon-optimized cDNAs encoding HLA-G1 and HLA-G5 isoforms one week prior to the induction of experimental autoimmune uveitis (EAU). AAV-mediated expression of the HLA-G-1 and -5 transgenes in the targeted ocular tissues following a single intravitreal injection of AAV-HLA-G1/5 significantly decreased clinical and histopathological inflammation scores compared to untreated EAU eyes (p < 0.04). Thus, localized ocular gene delivery of AAV-HLA-G1/5 may reduce the off-target risks and establish a long-term immunosuppressive effect that would serve as an effective and novel therapeutic strategy for NIU, with the potential for applications to additional ocular immune-mediated diseases.

Morphological characterization and multi-locus DNA sequence analysis of fungal isolates obtained from 32 clinical cases of equine fungal keratitis (FK) was performed to identify species and determine associations with antifungal susceptibility, response to therapy and clinical outcome. Two species of Aspergillus ( A . flavus and A . fumigatus ) and three species of Fusarium ( F . falciforme , F . keratoplasticum , and F . proliferatum ) were the most common fungi isolated and identified from FK horses. Most (91%) equine FK Fusarium nested within the Fusarium solani species complex (FSSC) with nine genetically diverse strains/lineages, while 83% of equine FK Aspergillus nested within the A . flavus clade with three genetically diverse lineages. Fungal species and evolutionary lineage were not associated with clinical outcome. However, species of equine FK Fusarium were more likely ( p = 0.045) to be associated with stromal keratitis. Species of Aspergillus were more susceptible to voriconazole and terbinafine than species of Fusarium , while species of Fusarium were more susceptible to thiabendazole than species of Aspergillus . At the species level, A . fumigatus and A . flavus were more susceptible to voriconazole and terbinafine than F . falciforme . Natamycin susceptibility was higher for F . falciforme and A . fumigatus compared to A . flavus . Furthermore, F . falciforme was more susceptible to thiabendazole than A . flavus and A . fumigatus . These observed associations of antifungal sensitivity to natamycin, terbinafine, and thiabendazole demonstrate the importance of fungal identification to the species rather than genus level. The results of this study suggest that treatment of equine FK with antifungal agents requires accurate fungal species identification.

Background Patients and the public have an integral role in educating healthcare professionals. Authentic partnerships between higher education institutions and patients and the public are essential. This study examined key stakeholders’ views, experiences and expectations of patient and public involvement (PPI) including the nature of the involvement and requirements for partnership. Methods Purposive and snowball sampling was used to recruit key stakeholders, including patients and members of the public involved in health professions education, and academics interested in PPI. Focus groups were held with patient and public participants, providing the opportunity to gain multiple perspectives in an interactive group setting. Academics with an interest in PPI were interviewed using a semi-structured approach. Topic guides were derived from the literature and piloted prior to data collection. Focus groups and interviews were conducted until data saturation was achieved. All data was audio-recorded, transcribed, anonymised and thematically analysed. Results Four focus groups were conducted involving 23 patient and public participants (median number of participants per focus group of 6). Nine interviews were conducted with academics (face-to-face [n = 8] or by telephone [n = 1]). Five themes were developed: previous experiences of PPI, training requirements, challenges/barriers to PPI, facilitators of PPI and future ideas for PPI. All participants held positive views of the value of PPI. Participants had mixed views in terms of training, which depended on the level of involvement, but similar views on the challenges and facilitators for PPI in education. There was agreement that PPI requires institutional vision and investment to build strong relationships and a culture of PPI best practice. Conclusions There is a need for more strategic and formal involvement of patients and the public to ensure that that PPI becomes sustainably embedded in health professions education.