Comprehensive proteomic profiling and quantitation of normal and lens-induced myopic chick vitreous using the next generation gel-free mass spectrometry

Myopia (shortsightedness) is a multifactorial condition which is resulted when an eye has grown too long for its focus. It is regards as the most common refractive error which often occurs at an early age and it usually progress over the years. The prevalence of myopia is alarmingly high and is up to 90% in some Asian countries. Both the prevalence and severity of myopia are growing worldwide. High myopia can lead to many sight-threatening ocular complications. In fact, myopic retinal degeneration is one of the leading causes of blindness in Hong Kong. As the myopic population continues to rise, it is feared that the number of visual impairments will escalate drastically. Despite that a large number of clinical and animal studies were conducted in the past, evidence–based methods for prevention or arrest of this disorder remain hampered by the lack of clear knowledge of the pathogenesis of myopia. Proteomic approach provides molecular "snap-shots" in which thousands of cellular proteins can be profiled, catalogued and compared efficiently. Modern advances in proteomic methods have enhanced our knowledge in many diseases for both diagnostic and therapeutic purposes. By comparing changes between normal and myopic tissues, key biochemical pathways in myopia may be revealed. In addition, protein phosphorylation is currently regarded as one of the most important post-translational modifications found in eukaryotes. It is a key mechanism of cellular signaling pathways and has been implicated in the development of a number of human diseases. However, there is still no published data on the possible protein modifications involved in myopia. Vitreous is known to be significantly altered during the myopic eye growth. Recent breakthrough in Liquid Chromatography/Mass Spectrometry (LCMS)-based profiling technique streamline with the tremendous development in bioinformatics tools offer sensitive and comprehensive analysis at high throughput which is nearly impossible 5 years ago. We aim to provide the first protein profiling of chick vitreous during the normal emmetropization. Applying isobaric labeled and novel label-free proteomic approach, we also aim to investigate the differential protein expressions as well as the phosphorproteomics in vitreous in response to the myopic growth and during recovery. More tissue specific data will provide a clearer picture about biochemical pathways that regulate the elongation of eyeball. This proposed pioneer proteomic work using the well-established chick model will shed important light on the mechanism of eye growth as well as open up new molecular targets for drug treatment for myopia.