Contacts
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).
Research Projects
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.
Research interests
- Retinal Degeneration
- Age-Related Macular Degeneration
- Novel Therapeutic Interventions
- MicroRNA
- Inflammation
Groups
Projects
- Principal investigator, MicroRNA as diagnostics and therapeutics for retinal degenerations
- Principal investigator, The benefits of exercise for retinal health and reducing retinal degenerations
- Principal investigator, Development of new animal models for retinal degenerations
- Principal investigator, Exosomes in retinal degenerations
- Principal investigator, Novel therapeutics to reduce the progression of retinal degenerations
- Researcher, Integration of single-cell and spatial transcriptomics underlies the molecular disparity in age-related macular degeneration mice eye
- Supervisor, 670nm Red Light as a treatment for Retinopathy of Prematurity (Phase 1 Clinical Trial)
- Supervisor, Optimising the dose of 670nm light therapy for treatment of retinal degenerations
- Supervisor, Role of miRNA in retinal degeneration
- Supervisor, The role of oxidative stress in the progression of retinal degenerations
- Supervisor, The use of miRNA as potential therapeutic targets in diseases causing retinal degenerations
- Fernando, N.*, Wooff, Y.*, Aggio-Bruce, R., Chu-Tan, J.A., Jiao, H., Dietrich, C., Rutar, M., Rooke, M., Menon, D., Eells, J.T., Valter, K., Board, P.G., Provis, J., Natoli, R. Photoreceptor survival is regulated by GSTO1-1 in the degenerating retina. Invest. Ophthalmol. Vis. Sci., 2018. 59(11) p. 4362-4374.
- 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-1β promotes chemokine expression by Muller cells and RPE in focal retinal degeneration', Molecular Neurodegeneration, vol. 12, pp. 1-11pp.
- Natoli, R, Fernando, N, Jiao, H et al 2017, 'Retinal Macrophages Synthesize C3 and Activate Complement in AMD and in Models of Focal Retinal Degeneration', Investigative Ophthalmology and Visual Science, vol. 58, no. 7, pp. 2977-2990pp.
- Lamb, T, Patel, H, Chuah, A et al 2016, 'Evolution of Vertebrate Phototransduction: Cascade Activation', Molecular Biology and Evolution, vol. 33, no. 8, pp. 2064-2087.
- Natoli, R, Jiao, H, Barnett, N et al 2016, 'A model of progressive photo-oxidative degeneration and inflammation in the pigmented C57BL/6J mouse retina', Experimental Eye Research, vol. 147, pp. 114-127.
- Chu-Tan, J, Rutar, M, Saxena, K et al 2016, 'Efficacy of 670 nm Light Therapy to Protect against Photoreceptor Cell Death Is Dependent on the Severity of Damage', International Journal of Photoenergy, vol. 2016, pp. 1-13.
- Fernando, N, Natoli, R, Valter, K et al 2016, 'The broad-spectrum chemokine inhibitor NR58-3.14.3 modulates macrophage-mediated inflammation in the diseased retina', Journal of Neuroinflammation, vol. 13, pp. -.
- Natoli, R, Rutar, M, Lu, Y et al 2016, 'The Role of Pyruvate in Protecting 661W Photoreceptor-Like Cells Against Light-Induced Cell Death', Current Eye Research, vol. Published online: 23 May 2016.
- Saxena, K, Rutar, M, Provis, J et al 2015, 'Identification of miRNAs in a model of retinal degenerations', Investigative Ophthalmology and Visual Science, vol. 56, no. 3, pp. 1820-1829.
- Kent, A, Broom, M, Parr, V et al 2015, 'A safety and feasibility study of the use of 670?nm red light in premature neonates', Journal of Perinatology, vol. 35, no. 493-496.
- Jiao, H, Natoli, R, Valter, K et al 2015, 'Spatiotemporal cadence of macrophage polarisation in a model of light-induced retinal degeneration', PLOS ONE (Public Library of Science), vol. 10, no. 12, pp. -.
- Rutar, M, Natoli, R, Chia, R et al 2015, 'Chemokine-mediated inflammation in the degenerating retina is coordinated by Müller cells, activated microglia, and retinal pigment epithelium', Journal of Neuroinflammation, vol. 12, no. 8, pp. 1-15.
- Giacci, M, Wheeler, L, Lovett, S et al 2014, 'Differential effects of 670 and 830nm red near infrared irradiation therapy: A comparative study of optic nerve injury, retinal degeneration, traumatic brain and spinal cord injury', PLOS ONE (Public Library of Science), vol. 9, no. 8, pp. 1-15.
- Barbosa, MS, Natoli, R, Valter, K et al 2014, 'Integral-geometry characterization of photobiomodulation effects on retinal vessel morphology', Biomedical Optics Express, vol. 5, no. 7, pp. 2317-2332.
- Rutar, M, Valter, K, Natoli, R et al 2014, 'Synthesis and propagation of complement C3 by microglia/monocytes in the aging retina', PLOS ONE (Public Library of Science), vol. 9, no. 4, pp. 1-10.
- Valter, K, Albarracin, R, Natoli, R et al 2014, '670nm - A stop sign for retinal degenerations?', 2014 WALT Biennial Congress and NAALT Annual Conference, ed. Laakso E.-L., Conference Organising Committee, TBC, pp. 33-38.
- Fitzgerald, M, Hodgetts, S, Van Den Heuvel, C et al 2013, 'Red/near-infrared irradiation therapy for treatment of central nervous system injuries and disorders', Reviews in the Neurosciences, vol. 24, no. 2, pp. 205-226.
- Albarracin, R, Natoli, R, Rutar, M et al 2013, '670 nm light mitigates oxygen-induced degeneration in C57BL/6J mouse retina', BMC Neuroscience, vol. 14, pp. -.
- Natoli, R, Valter, K, Barbosa, MS et al 2013, '670nm Photobiomodulation as a Novel Protection against Retinopathy of Prematurity: Evidence from Oxygen Induced Retinopathy Models', PLOS ONE, vol. 8, no. 8, pp. e72135.
- Munoz-Erazo, L, Natoli, R, Provis, J et al 2012, 'Microarray analysis of gene expression in West Nile virus-infected human retinal pigment epithelium', Molecular Vision, vol. 18, pp. 730-743.
- Rutar, M, Natoli, R & Provis, J 2012, 'Small interfering RNA-mediated suppression of Ccl2 in Müller cells attenuates microglial recruitment and photoreceptor death following retinal degeneration', Journal of Neuroinflammation, vol. 9.
- Natoli, R, Provis, J, Valter, K et al 2012, '670 NM Red Light: Protection Against Retinopathy of Prematurity', 43rd Annual Scientific Congress - Sharing the Vision, Wiley Online Library , Brisbane / online, p. 87.
- Natoli, R, Valter, K, Soares Barbosa, M et al 2015, '591: Can 670Nm Red Light Protect Against Retinopathy of Prematurity and Reduce Lung Injury in a Neonatal Animal Model?', European Academy of Paediatric Societies (EAPS 2012), BMJ Publishing Group, United Kingdom.
- Rutar, M, Natoli, R, Albarracin, R et al 2012, '670-nm light treatment reduces complement propagation following retinal degeneration', Journal of Neuroinflammation, vol. 9, no. 257, pp. -.
- Rutar, M, Natoli, R, Provis, J et al 2012, 'Complement activation in retinal degeneration', in Matthew M. LaVail, John D. Ash Robert E. Anderson, Joe G. Hollyfi eld Christia (ed.), Retinal Degenerative Diseases, Springer, United States, pp. 31-36.
- Rutar, M, Natoli, R, Kozulin, P et al 2011, 'Analysis of complement expression in light-induced retinal degeneration: Synthesis and deposition of C3 by microglia/macrophages is associated with focal photoreceptor degeneration', Investigative Ophthalmology and Visual Science, vol. 52, no. 8, pp. 5347-5358.
- Rutar, M, Natoli, R, Valter, K et al 2011, 'Early focal expression of the chemokine Ccl2 by Muller cells during exposure to damage-inducing bright continuous light', Investigative Ophthalmology and Visual Science, vol. 52, no. 5, pp. 2379-2388.
- Ebeling, W, Natoli, R & Hemmi, J 2010, 'Diversity of Color Vision: Not All Australian Marsupials Are Trichromatic', PLoS ONE (Public Library of Science), vol. 5, no. 12, pp. e14231.
- Kozulin, P, Natoli, R, Bumsted O'Brien, K et al 2010, 'The cellular expression of anti-angiogenic factors in fetal primate retina', Investigative Ophthalmology & Visual Science, vol. 51, no. 8, pp. 4298-4306.
- Natoli, R, Valter, K, Chrysostomou, V et al 2010, 'Morphological, functional and gene expression analysis of the hyperoxic mouse retina', Experimental Eye Research, vol. 92, pp. 306-314.
- Natoli, R, Zhu, Y, Valter, K et al 2010, 'Gene and noncoding RNA regulation underlying photoreceptor protection: microarray study of dietary antioxidant saffron and photobiomodulation in rat retina', Molecular Vision, vol. 16, pp. 1801-1822.
- Zhu, Y, Natoli, R, Valter, K et al 2010, 'Differential gene expression in mouse retina related to regional differences in vulnerability to hyperoxia', Molecular Vision, vol. 16, pp. 740-755.
- Zhu, Y, Natoli, R, Valter, K et al 2010, 'Microarray Analysis of Hyperoxia Stressed Mouse Retina: Differential Gene Expression in the Inferior and Superior Region', in Robert E Anderson, Joe G Hollyfield & Matthew M LaVail (ed.), Retinal Degenerative Diseases: Laboratory and Therapeutic Investigations, Landes Bioscience/Springer Science+Business Media, Berlin, pp. 217-222.
- Kozulin, P, Natoli, R, Madigan, M et al 2009, 'Gradients of Eph-A6 expression in primate retina suggest roles in both vascular and axon guidance', Molecular Vision, vol. 15, pp. 2649-2662.
- Shelley, E, Madigan, M, Penfold, P et al 2009, 'Cone Degeneration in Aging and Age-Related Macular Degeneration', Archives of Ophthalmology, vol. 127, no. 4, pp. 483-492.
- Kozulin, P, Natoli, R, Bumsted O'Brien, K et al 2009, 'Differential expression of anti-angiogenic factors and guidance genes in the developing macula', Molecular Vision, vol. 15, pp. 45-59.
- Hendrickson, A, Bumsted O'Brien, K, Natoli, R et al 2008, 'Rod photoreceptor differentiation in fetal and infant human retina', Experimental Eye Research, vol. 87, pp. 415-426.
- Natoli, R, Provis, J, Valter, K et al 2008, 'Expression and role of the early-response gene Oxr1 in the hyperoxia-challenged mouse retina', Investigative Ophthalmology and Visual Science, vol. 49, no. 10, pp. 4561-4567.
- Natoli, R, Provis, J, Valter, K et al 2008, 'Gene regulation induced in the C57BL/6J mouse retina by hyperoxia: a temporal microarray study', Molecular Vision, vol. 14, pp. 1983-1994.
- Kozulin, P, Natoli, R & Provis, J 2006, 'Expression of EPH receptors and ephrins in developing primate retina', International Congress of Eye Research 2006, Conference Organising Committee, na, p. 1.
- Kozulin, P, Ohms, S, Natoli, R et al 2006, 'Microarray analysis of gene expression in the developing Fovea', Australasian Ophthalmic & Viual Sciences Meeting 2006, ed. Ophthalmic Research Institute of Australia, Conference Organising Committee, ANU Canberra, p. 1.
- Natoli, R, Provis, J & Stone, J 2006, 'OXR-1 in the Hyperoxic C57BL/6J Mouse Retina', Australasian Ophthalmic & Viual Sciences Meeting 2006, ed. Ophthalmic Research Institute of Australia, Conference Organising Committee, ANU Canberra, p. 40.
- Cornish, E, Madigan, M, Natoli, R et al 2005, 'Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina', Visual Neuroscience, vol. 22, pp. 447-459.
- Cornish, E, Natoli, R, Hendrickson, A et al 2004, 'Differential distribution of fibroblast growth factor receptors (FGFRs) on foveal cones: FGFR-4 is an early marker of cone photoreceptors', Molecular Vision, vol. 10, pp. 1-14.
