I am interested in novel strategies that reduce the severity and progression of dry Age-related Macular Degeneration (AMD). I aim to understand the factors that cause photoreceptors to die, and identify novel ways to protect them from degeneration. My recent work focuses on the role of microRNA (miRNA) in the degenerating retina, and examines their potential use as therapeutics. This ground-breaking work has been funded by competitive funding agencies (Ophthalmic Research Institute of Australia, Retina Australia and NHMRC) as well as industry (Thermo Fisher Scientific, Beta Therapeutics, EyeCo, MuPharma and Bayer) and through innovation investment funding (Discovery Translational Fund). I have also developed a non-invasive treatment strategy to revolutionise the management of premature infants at risk of developing Retinopathy of Prematurity (ROP) and increasing survivability, currently and ongoing collaboration with members of the ANU Medical School and Canberra Hospital.
I have contributed to 49 publications, as well as presented at international and national conferences including the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, International Society for Eye Research (ISER) Germany and the International Symposium on Retinal Degeneration, Germany; I was awarded a Travel Grant to attend and present at the XVIth International Symposium on Retinal Degeneration in Japan in 2016. I consider research-led education as an integral part of a researcher’s career. I am a lecturer in genetics and cell biology in the ANU Medical School, supervise/co-supervise a number of PhD and honours students. I helped to establish, and convene the JCSMR HDR Mentoring Program, as well as am 1st Year Coordinator for the ANU Medical School. In 2017, I established Clear Vision Research to support the next generation of vision researchers (www.clearvisionresearch.com).
1. MicroRNA as regulators of inflammation and the inflammasome
The most common cause of blindness in Australia is Age-Related Macular Degeneration (AMD), costing the Australian economy ~5 billion dollars annually and ~350 billion dollars globally. The study of miRNAs will provide a new avenue for drug discovery for diseases such as AMD, and have applications for other neurodegenerative diseases. MiRNA are small non-coding RNA molecules that post transcriptionally regulate gene expression and are considered the ‘master regulators’ of gene transcription. We are looking at using miRNA as therapeutics to reduce inflammation and inflammasome activation in retinal degenerations.
2. Molecular and epigenetic regulation by recruited and resident monocytes in retinal degeneration
Dysregulation of microglia/macrophages is a key pathogenic mechanism underlying many age-related neurodegenerative diseases, highlighting the importance of understanding how these cells respond to ageing and stress. We are deciphering the molecular profile of the resident microglia and recruited macrophages in the retina, to further understand their role in disease progression and to explore the possibility of reprogramming ageing cells to a quiescent state in order to preserve retinal function.
3. Novel therapeutics for reducing the progression of Age-Related Macular Degeneration
Current projections indicate that by 2030, 1.7 million people in Australia will suffer vision loss due to Age-Related Macular Degeneration (AMD), with a major contribution being the current lack of treatment options available for the more prevalent atrophic or ‘dry’ form of the disease. We are exploring a number of therapeutic options, including gene-based therapies, non-invasive therapeutics and novel compounds. We are actively engaging with commercial partners to help develop strategies to reduce inflammation and cell death in all forms of AMD.
4. The role of complement in retinal degeneration
Dysregulation of complement is strongly associated with Age-related Macular Degeneration (AMD). However, the events that lead to complement activation are poorly understood, and how complement causes photoreceptor cell loss is not known. We have developed a unique mouse model of photo-oxidative retinal damage, which mimics facets of the more prevalent form of AMD, ‘dry’ AMD, for which there are no current treatments. Using this model and human tissue we have found that retinal microglia are responsible for depositing complement, and are exploring if inhibition of this pathway is protective against progressive retinal cell death.
- Jiao, H., Rutar, M., Fernando, N., Yednock, T., Sankaranarayanan, Aggio-Bruce, R., Provis, J., Natoli, R. Subretinal macrophages produce classical complement activator C1q leading to the progression of focal retinal degeneration. Mol. Neurodegener., 2018. 13, 45.
- Chu-Tan, J.A., Rutar, M., Saxena, K., Aggio-Bruce, R., Essex, R.W., Valter, K., Jiao, H., Fernando, N., Wooff, Y., Madigan, M.C., Provis, J., Natoli, R. MicroRNA-124 dysregulation is associated with retinal inflammation and photoreceptor death in the degenerating retina. Invest. Ophthalmol. Vis. Sci., 2018. 59(10) p. 4094-4105.
- Natoli, R., E. Mason, H. Jiao, A. Chuah, H. Patel, N. Fernando, K. Valter, C.A. Wells, J. Provis, and M. Rutar, Dynamic Interplay of Innate and Adaptive Immunity During Sterile Retinal Inflammation: Insights From the Transcriptome. Front Immunol, 2018. 9: p. 1666.
- Natoli, R.*, N. Fernando*, T. Dahlenburg*, H. Jiao, R. Aggio-Bruce, N.L. Barnett, J.M. Chao de la Barca, G. Tcherkez, P. Reynier, J. Fang, J.A. Chu-Tan, K. Valter, J. Provis, and M. Rutar, Obesity-induced metabolic disturbance drives oxidative stress and complement activation in the retinal environment. Mol Vis, 2018. 24: p. 201-217.
- Natoli, R. and N. Fernando, MicroRNA as Therapeutics for Age-Related Macular Degeneration. Adv Exp Med Biol, 2018. 1074: p. 37-43
- Lu, Y.Z., N. Fernando, R. Natoli, M. Madigan, and K. Valter, 670nm light treatment following retinal injury modulates Muller cell gliosis: Evidence from in vivo and in vitro stress models. Exp Eye Res, 2018. 169: p. 1-12.
- Fernando, N., R. Natoli, T. Racic, Y. Wooff, J. Provis, and K. Valter, The use of the vaccinia virus complement control protein (VCP) in the rat retina. PLoS One, 2018. 13(3): p. e0193740.
- Natoli, R, Fernando, N, Madigan, M et al 2017, 'Microglia-derived IL-1Î² promotes chemokine expression by Muller cells and RPE in focal retinal degeneration', Molecular Neurodegeneration, vol. 12, pp. 1-11pp.