Detection of Apoptosing Retinal Cells in Glaucoma Diagnosis

Detection of Apoptosing Retinal cells in Glaucoma diagnosingStudy ProposalInvestigating a possible correlation between DARC (Detection of Apoptosing Retinal Cells) and Psychophysical methods (e.g. course Sensitivity, illusion Vision, LogMAR Visual Acuity in different contrast levels) in Glaucoma diagnosis and assessing treatment efficacy.BackgroundGlaucoma is a neurodegenerative nerve center disease and one of the major causes offor blindness in developed countries. It is a chronic degenerative disease of the optic nerve, which has been characterised by a progressive loss of retinal ganglion cells (RGCs) and their axons (Sommer, 1989). Glaucoma is a collective bourn for a complex group of conditions that cause progressive optic neuropathy, which may result in permanent loss of optic function.E1 Therefore, assessment of visual function is essential in diagnosis and treatment of Glaucoma.Although some(prenominal) diagnostic appliances have been developed to detect and monitor this disease, none is sensitive enough to commit it at a preclinical stage or to distinguish small changes in retinal health in a relatively short periods (Normando et al., 2013)In Glaucoma, irreversible visual changes may occur before neural damages atomic number 18 discovered. The catching of glaucomatous structural damage might happen before, during and after glaucomatous visual guinea pig of honor defects findings (Kass et al., 2002). Clinical assessment of visual function in parafoveal regions is mostly dependent on the examination of visual fields by using standard perimetry (Rauscher et al., 2013). Perimetry plots often do not represent full boundary of visual loss as conventional field assessments only examine a single own at the location tested, which usually is the differential light threshold. Although, outcome for absolute thresholds of flashed stimuli is useful but frequently these findings are the final component of visual function that are affected in disease . It should be interpreted into consideration that visual field defects cannot be detected until 20-40% of retinal ganglion cells (RGCs) which are the key cells associated with the development of irreversible blindness in glaucoma, have already been lost (Guo and Cordeiro, 2008). In m some(prenominal) of the eye disease, sensitivity for detection of fine spatial detail and colour attributeals can be damaged prior to visual field loss (Barbur and Konstantakopoulou, 2012).In studies such as (Rauscher et al., 2013) colour thresholds revealed the highest sensitivity to early glaucomatous changes and Red/Green losings tended to happen before perimetric loss of binocular visual field sensitivity. It should be noted that simple measures of perimetriy are not sensitive enough to detect selective loss of specific visual attributes and therefore tumble to show a strong correlation with Quality Of Life (QOL) measures.Moreover, the ability to differentiate contrast plays an essential role in patients everyday vision and quality of life. Contrast sensitivity testing can identify many ocular diseases and provides additional useful clinical in material bodyation to standard visual acuity assessments (Richman et al., 2013).Additionally, a new noninvasive real- cartridge clip imaging technology, has recently been developed which is named DARC (Detection of Apoptosing Retinal Cells). Apoptosis is a form of programmed cell death that is involved in both pathological and physiological processes throughout the body. Although, Apoptosis plays a vital role in normal development and ageing but deregulation of this process is responsible for(p) for many disease including neurodegenerative disorders. Therefore, in vivo imaging of caspase-mediated cell death may prove a useful tool for both laboratory research and clinical diagnostics (Galvao et al., 2013)DARC visualizes single RGC, which undergo apoptosis, as the earliest sign of glaucoma. Use of fluorescent annexin A5 is one of t he most widely accepted in vitro assay for apoptotic cells (Normando et al., 2013). DARC is a non-radioactive surface that can evaluate the efficiency of the treatments by monitoring RGC apoptosis in the same living eye over time by using fluorescently labeled annexin 5 and confocal laser scanning ophthalmoscopy. DARC uses unique visual properties of the eye for direct microscopic observation of cellular processes in the retina. DARC has been used to assess different neuroprotective therapies in glaucoma-related animal models and demonstrated to be a useful tool in screening neuroprotective strategies. As DARC straight evaluates the RGC death process, it will potentially provide a meaningful clinical end point. DARC can be used in tracking disease, assessing treatment efficacy and may lead to the early identification of patients with glaucoma (Cordeiro et al., 2010 Cordeiro et al., 2011 Guo and Cordeiro, 2008 Normando et al., 2013).DARC uses a novel automated algorithm, which ena bles accurate quantification of apoptosing RGCs and is highly comparable to manual counting. This appears to minimise operator-bias and at the same time being both fast and reproducible. Quantification of apoptosing retinal cells may prove to be a valuable method, specially in relation to translation in the clinic now that a Phase I clinical streamlet of DARC in glaucoma patients is due to start shortly (Bizrah et al., 2014).3 year plan1st Year ethics approvalPre-Screening patients with glaucoma for suitability using LogMAR visual acuity in low contrast level and any available visual field findings2nd YearRecruiting candidatesStudy both psychophysical methods (Contrast sensitivity and colour vision) and DARCthird YearData analyzingWriting upExpecting outcome make better evaluation of sensation in patients with glaucomaBetter evaluation of Quality Of Life (QOL)Better evaluation of the most suitable method for early diagnostic and follow-up treatments in glaucomaPossible diagnostic and follow-up applications of the selected methods for other neurodegenerative disease such as Alzheimer and ParkinsonReferencesBarbur JL, Konstantakopoulou E (2012) Changes in color vision with decreasing light level separating the effects of normal aging from disease. J Opt Soc Am A Opt Image Sci Vis 29A27A35Bizrah, M., S. C. Dakin, L. Guo, F. Rahman, M. Parnell, E. Normando, S. Nizari, B. Davis, A. Younis, and M. F. Cordeiro, 2014, A semi-automated technique for labeling and counting of apoptosing retinal cells BMC Bioinformatics, v. 15, p. 169.Cordeiro, M. F., L. Guo, K. M. Coxon, J. Duggan, S. Nizari, E. M. Normando, S. L. Sensi, A. M. Sillito, F. W. Fitzke, T. E. Salt, and S. E. Moss, 2010, Imaging multiple phases of neurodegeneration a novel approach to assessing cell death in vivo Cell wipeout Dis, v. 1, p. e3.Cordeiro, M. F., C. Migdal, P. Bloom, F. W. Fitzke, and S. E. Moss, 2011, Imaging apoptosis in the eye Eye (Lond), v. 25, p. 545-53.Galvao, J., B. M. Davis, and M. F. Cordeiro, 2013, In vivo imaging of retinal ganglion cell apoptosis Curr Opin Pharmacol, v. 13, p. 123-7.Guo, L., and M. F. Cordeiro, 2008, Assessment of neuroprotection in the retina with DARC Prog Brain Res, v. 173, p. 437-50.Kass, M. A., D. K. Heuer, E. J. Higginbotham, C. A. Johnson, J. L. Keltner, J. P. Miller, R. K. Parrish, M. R. Wilson, and M. O. Gordon, 2002, The Ocular Hypertension Treatment Study a randomized struggle determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma Arch Ophthalmol, v. 120, p. 701-13 discussion 829-30.Lek, J. J., A. J. Vingrys, and A. M. McKendrick, 2014, quick contrast adaptation in glaucoma and in aging Invest Ophthalmol Vis Sci, v. 55, p. 3171-8.Normando, E. M., L. A. Turner, and M. F. Cordeiro, 2013, The potential of annexin-labelling for the diagnosis and follow-up of glaucoma Cell Tissue Res, v. 353, p. 279-85.Rauscher, F. G., C. M. Chisholm, D. F. Edgar, and J. L. Barbur, 2013, Asse ssment of novel binocular colour, motion and contrast tests in glaucoma Cell Tissue Res, v. 353, p. 297-310.Richman, J., G. L. Spaeth, and B. Wirostko, 2013, Contrast sensitivity basics and a critique of currently available tests J Cataract Refract Surg, v. 39, p. 1100-6.Sommer, A., 1989, Intraocular pressure and glaucoma Am J Ophthalmol, v. 107, p. 186-8.E1it looks too similar to the sentence in the article below. Could you please rephrase?http//openaccess.city.ac.uk/3294/1/ origin version Edgar DF paper 1432-0878 15 03 14.pdf