Molecular basis of glaucoma and its therapeutical analysis in Pakistan: an overview

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Luqman Khan Muhammad Ali Muhammad Qasim Farhat Jabeen Basharat Hussain


The human eye is an organ of vision. It plays a prime role in life, gives us the sense of sight, and enables to understand about the world around us. Visualization and interpretation of colors, shapes and dimensions of numerous objects is made possible by eye. Inherited eye diseases comprise 1/3 of all reported human genetic disorders. This review will focus on Glaucoma which comprises a predictable visual illnesses concerning optic nerve deterioration and if remains without any cure can result in failure in eyesight. The optical nerve injure comprises deterioration of the retinal ganglion cells (RGCs). Glaucoma represents a heterogeneous group of optic neuropathies with a complex genetic basis. These neuropathies gradually reduce vision without warning and often without symptoms. Different forms of glaucoma share some common clinical manifestations that usually include specific abnormal appearance of the optic nerve head, characteristic loss of visual field and chronic painless progression. Glaucoma is a progressive optical neuropathy considered by optical disc changes, nerve fiber film break, and visual field defects. Present-day treatment preferences predominantly targeting at reducing IOP by making use of pharmaceutical means, laser treatment and surgical procedure. Developed conducts target neuroprotection with vaccines, the hang-up of NO synthesis and apoptosis. Attaining a better appreciative of the pathogenesis can support in the improvement of novel handling options and, perhaps, even a remedy for glaucoma. There are more than 1.8million glaucoma patients in Pakistan and almost half of them have already lost their eyesight, permanently, due to delay in diagnosis and treatment. About 90% population in the country has no awareness about this disease, resultantly; more and more people are becoming permanently blind in Pakistan due to untreated glaucoma.


Abu-Amero, K.K., Morales, J., Osman, M.N., and Bosley, T.M. (2007). Nuclear and mitochondrial analysis of patients with primary angle-closure glaucoma. Investigative ophthalmology & visual science 48, 5591-5596.
Adamus, G., Sugden, B., Shiraga, S., Timmers, A.M., and Hauswirth, W.W. (2003). Anti-apoptotic effects of CNTF gene transfer on photoreceptor degeneration in experimental antibody-induced retinopathy. Journal of autoimmunity 21, 121-129.
Akarsu, A.N., Turacli, M.E., Aktan, S.G., Barsoum-Homsy, M., Chevrette, L., Sayli, B.S., and Sarfarazi, M. (1996). A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region. Human molecular genetics 5, 1199-1203.
Alguire, P. (1990). The Eye Chapter 118 Tonometry> Basic Science. Walker HK, Hall WD, Hurst JW Clinical methods: the history, physical, and laboratory examinations.
Ali, M., McKibbin, M., Booth, A., Parry, D.A., Jain, P., Riazuddin, S.A., Hejtmancik, J.F., Khan, S.N., Firasat, S., and Shires, M. (2009). Null mutations in LTBP2 cause primary congenital glaucoma. The American Journal of Human Genetics 84, 664-671.
Alsbirk, P. (1975). ANTERIOR CHAMBER DEPTH AND PRIMARY ANGLE‐CLOSURE GLAUCOMA. Acta ophthalmologica 53, 436-449.
Alward, W.L., Fingert, J.H., Coote, M.A., Johnson, A.T., Lerner, S.F., Junqua, D., Durcan, F.J., McCartney, P.J., Mackey, D.A., and Sheffield, V.C. (1998). Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A). New England Journal of Medicine 338, 1022-1027.
Amerasinghe, N., Zhang, J., Thalamuthu, A., He, M., Vithana, E.N., Viswanathan, A., Wong, T.Y., Foster, P.J., and Aung, T. (2011). The heritability and sibling risk of angle closure in Asians. Ophthalmology 118, 480-485.
Bakalash, S., Kessler, A., Mizrahi, T., Nussenblatt, R., and Schwartz, M. (2003). Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma. Investigative ophthalmology & visual science 44, 3374-3381.
Baptiste, D.C., Hartwick, A.T., Jollimore, C.A., Baldridge, W.H., Seigel, G.M., and Kelly, M.E. (2004). An investigation of the neuroprotective effects of tetracycline derivatives in experimental models of retinal cell death. Molecular pharmacology 66, 1113-1122.
Bartlett, H., and Eperjesi, F. (2004). An ideal ocular nutritional supplement? Ophthalmic and Physiological Optics 24, 339-349.
Bashir, R., Tahir, H., Yousaf, K., Naz, S., and Naz, S. (2015). Homozygous p. G61E mutation in a consanguineous Pakistani family with co-existence of juvenile-onset open angle glaucoma and primary congenital glaucoma. Gene 570, 295-298.
Bejjani, B.A., Stockton, D.W., Lewis, R.A., Tomey, K.F., Dueker, D.K., Jabak, M., Astle, W.F., and Lupski, J.R. (2000). Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus. Human molecular genetics 9, 367-374.
Bourne, R.R., Taylor, H.R., Flaxman, S.R., Keeffe, J., Leasher, J., Naidoo, K., Pesudovs, K., White, R.A., Wong, T.Y., and Resnikoff, S. (2016). Number of People Blind or Visually Impaired by Glaucoma Worldwide and in World Regions 1990–2010: A Meta-Analysis. PloS one 11, e0162229.
Boyd, Z.S., Kriatchko, A., Yang, J., Agarwal, N., Wax, M.B., and Patil, R.V. (2003). Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of retinal ganglion cells in response to stress. Investigative ophthalmology & visual science 44, 5206-5211.
Brubaker, R. (2003). Introduction: three targets for glaucoma management. Survey of ophthalmology 48, S1.
Challa, P. (2008). Glaucoma genetics. International ophthalmology clinics 48, 73.
Cong, Y., Guo, X., Liu, X., Cao, D., Jia, X., Xiao, X., Li, S., Fang, S., and Zhang, Q. (2009). Association of the single nucleotide polymorphisms in the extracellular matrix metalloprotease-9 gene with PACG in southern China.
Congdon, N.G., Quigley, H.A., Hung, P.T., Wang, T., and Ho, T. (1996). Screening techniques for angle‐closure glaucoma in rural Taiwan. Acta Ophthalmologica Scandinavica 74, 113-119.
Consoli, D., and Ramlogan, R. (2015). The silent thief of sight. Medical Innovation: Science, Technology and Practice, 142.
Dandona, L., Dandona, R., Mandal, P., Srinivas, M., John, R.K., McCarty, C.A., and Rao, G.N. (2000). Angle-closure glaucoma in an urban population in southern India: the Andhra Pradesh Eye Disease Study. Ophthalmology 107, 1710-1716.
Dandona, L., Williams, J.D., Williams, B.C., and Rao, G.N. (1998). Population-based assessment of childhood blindness in southern India. Archives of ophthalmology 116, 545-546.
Fan, B.J., and Wiggs, J.L. (2010). Glaucoma: genes, phenotypes, and new directions for therapy. The Journal of clinical investigation 120, 3064-3072.
Fatt, I., and Weissman, B.A. (2013). Physiology of the eye: an introduction to the vegetative functions (Butterworth-Heinemann).
Fechtner, R.D., and Realini, T. (2004). Fixed combinations of topical glaucoma medications. Current opinion in ophthalmology 15, 132-135.
Firasat, S., Riazuddin, S., Khan, S.N., and Riazuddin, S. (2008). Novel CYP1B1 mutations in consanguineous Pakistani families with primary congenital glaucoma.
Foster, P.J., Baasanhu, J., Alsbirk, P.H., Munkhbayar, D., Uranchimeg, D., and Johnson, G.J. (1996). Glaucoma in Mongolia: a population-based survey in Hövsgöl Province, northern Mongolia. Archives of ophthalmology 114, 1235-1241.
Foster, P.J., Oen, F.T., Machin, D., Ng, T.-P., Devereux, J.G., Johnson, G.J., Khaw, P.T., and Seah, S.K. (2000). The prevalence of glaucoma in Chinese residents of Singapore: a cross-sectional population survey of the Tanjong Pagar district. Archives of Ophthalmology 118, 1105-1111.
Gemenetzi, M., Yang, Y., and Lotery, A. (2012). Current concepts on primary open-angle glaucoma genetics: a contribution to disease pathophysiology and future treatment. Eye 26, 355-369.
Ghate, D., and Wang, X. (2015). Surgical interventions for primary congenital glaucoma. The Cochrane Library.
Gupta, R., Gupta, B., Kshitij, A., and Bala, A. (2014). Glaucoma Research: A Scientometric Study of Indian Publications Output, 2002-11. DESIDOC Journal of Library & Information Technology 34.
Heijl, A., Leske, M.C., Bengtsson, B., Hyman, L., Bengtsson, B., and Hussein, M. (2002). Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Archives of ophthalmology 120, 1268-1279.
Helmy, H. (2016). Combined trabeculotomy-trabeculectomy versus Ahmed valve implantation for refractory primary congenital glaucoma in Egyptian patients: a long-term follow-up. Electronic Physician 8, 1884.
Hirooka, K., Tokuda, M., Miyamoto, O., Itano, T., Baba, T., and Shiraga, F. (2004). The Ginkgo biloba extract (EGb 761) provides a neuroprotective effect on retinal ganglion cells in a rat model of chronic glaucoma. Current eye research 28, 153-157.
Huang, E.C., and Barocas, V.H. (2004). Active iris mechanics and pupillary block: steady-state analysis and comparison with anatomical risk factors. Annals of biomedical engineering 32, 1276-1285.
Janssen, S.F., Gorgels, T.G., Ramdas, W.D., Klaver, C.C., van Duijn, C.M., Jansonius, N.M., and Bergen, A.A. (2013). The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Progress in retinal and eye research 37, 31-67.
Kelliher, C., Kenny, D., and O’Brien, C. (2006). Trends in blind registration in the adult population of the Republic of Ireland 1996–2003. British journal of ophthalmology 90, 367-371.
Khan, A.O. (2011). Genetics of primary glaucoma. Current opinion in ophthalmology 22, 347-355.
Khaw, P., Shah, P., and Elkington, A. (2004). Glaucoma--2: treatment. BMJ 328, 156-158.
Kuehn, M.H., Wang, K., Roos, B., Stone, E.M., Kwon, Y.H., Alward, W.L., Mullins, R.F., and Fingert, J.H. (2011). Chromosome 7q31 POAG locus: ocular expression of caveolins and lack of association with POAG in a US cohort.
Kwon, Y.H., Fingert, J.H., Kuehn, M.H., and Alward, W.L. (2009). Primary open-angle glaucoma. New England Journal of Medicine 360, 1113-1124.
Lawrence, J.M. (2014). Pattern of ocular findings among patients aged 40 years and above attending eye clinic at Juba teaching hospital in Southern Sudan (University of Nairobi).
Lemij, H.G., Hoevenaars, J.G., van der Windt, C., and Baudouin, C. (2015). Patient satisfaction with glaucoma therapy: reality or myth? Clinical ophthalmology (Auckland, NZ) 9, 785.
Lin, Y., Wang, T., and Hung, P. (1997). Biometric study of acute primary angle-closure glaucoma. Journal of the Formosan Medical Association= Taiwan yi zhi 96, 908-912.
Lipton, S.A. (2003). Possible role for memantine in protecting retinal ganglion cells from glaucomatous damage. Survey of ophthalmology 48, S38-S46.
Maul, E., Strozzi, L., Muñoz, C., and Reyes, C. (1980). The outflow pathway in congenital glaucoma. American journal of ophthalmology 89, 667-675.
McKinnon, S.J., Lehman, D.M., Tahzib, N.G., Ransom, N.L., Reitsamer, H.A., Liston, P., LaCasse, E., Li, Q., Korneluk, R.G., and Hauswirth, W.W. (2002). Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model. Molecular Therapy 5, 780.
Micheal, S., Ayub, H., Islam, F., Siddiqui, S.N., Khan, W.A., Akhtar, F., Qamar, R., Khan, M.I., and den Hollander, A.I. (2015a). Variants in the ASB10 Gene Are Associated with Primary Open Angle Glaucoma. PloS one 10, e0145005.
Micheal, S., Ayub, H., Zafar, S.N., Bakker, B., Ali, M., Akhtar, F., Islam, F., Khan, M.I., Qamar, R., and Hollander, A.I. (2015b). Identification of novel CYP1B1 gene mutations in patients with primary congenital and primary open‐angle glaucoma. Clinical & experimental ophthalmology 43, 31-39.
Monemi, S., Spaeth, G., DaSilva, A., Popinchalk, S., Ilitchev, E., Liebmann, J., Ritch, R., Héon, E., Crick, R.P., and Child, A. (2005). Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22. 1. Human molecular genetics 14, 725-733.
Nemesure, B., He, Q., Mendell, N., Wu, S.Y., Hejtmancik, J.F., Hennis, A., and Leske, M.C. (2001). Inheritance of open‐angle glaucoma in the Barbados family study. American journal of medical genetics 103, 36-43.
Neufeld, A.H. (2004). Pharmacologic neuroprotection with an inhibitor of nitric oxide synthase for the treatment of glaucoma. Brain research bulletin 62, 455-459.
Osborne, N.N., Wood, J.P., Cupido, A., Melena, J., and Chidlow, G. (2002). Topical flunarizine reduces IOP and protects the retina against ischemia-excitotoxicity. Investigative ophthalmology & visual science 43, 1456-1464.
Pascolini, D., Mariotti, S., Pokharel, G., Pararajasegaram, R., Etya’ale, D., Négrel, A.-D., and Resnikoff, S. (2009). 2002 global update of available data on visual impairment: a compilation of population-based prevalence studies. Ophthalmic epidemiology.
Quigley, H.A. (1996). Number of people with glaucoma worldwide. British Journal of Ophthalmology 80, 389-393.
Quigley, H.A., and Broman, A.T. (2006). The number of people with glaucoma worldwide in 2010 and 2020. British journal of ophthalmology 90, 262-267.
Quigley, H.A., Congdon, N.G., and Friedman, D.S. (2001). Glaucoma in China (and worldwide): changes in established thinking will decrease preventable blindness. British Journal of Ophthalmology 85, 1271-1272.
Rauf, B., Irum, B., Kabir, F., Firasat, S., Naeem, M.A., Khan, S.N., Husnain, T., Riazuddin, S., Akram, J., and Riazuddin, S.A. (2016). A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in families of Pakistani descent. Human Genome Variation 3, 16021.
Resnikoff, S., Pascolini, D., Etya'ale, D., Kocur, I., Pararajasegaram, R., Pokharel, G.P., and Mariotti, S.P. (2004). Global data on visual impairment in the year 2002. Bulletin of the world health organization 82, 844-851.
Salmon, J.F. (1999). Predisposing factors for chronic angle-closure glaucoma. Progress in retinal and eye research 18, 121-132.
Sarfarazi, M. (1997). Recent advances in molecular genetics of glaucomas. Human molecular genetics 6, 1667-1677.
Sarfarazi, M., Akarsu, N.A., Hossain, A., Turacli, E.M., Aktan, G.S., Barsoum-Homsy, M., Chevrette, L., and Sayli, S.B. (1995). Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity. Genomics 30, 171-177.
Sarfarazi, M., Stoilov, I., and Schenkman, J.B. (2003). Genetics and biochemistry of primary congenital glaucoma. Ophthalmology Clinics 16, 543-554.
Schwartz, K., and Budenz, D. (2004). Current management of glaucoma. Current opinion in ophthalmology 15, 119-126.
Sohn, S., Im, J.-E., Kim, T.E., and Kee, C. (2013). Effect of heat shock protein 72 expression on etoposide-induced cell death of rat retinal ganglion cells. Korean Journal of Ophthalmology 27, 48-51.
Stoilov, I., Akarsu, A.N., and Sarfarazi, M. (1997). Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Human molecular genetics 6, 641-647.
Stoilov, I.R., Costa, V.P., Vasconcellos, J.P., Melo, M.B., Betinjane, A.J., Carani, J.C., Oltrogge, E.V., and Sarfarazi, M. (2002). Molecular genetics of primary congenital glaucoma in Brazil. Investigative ophthalmology & visual science 43, 1820-1827.
Stone, E.M., Fingert, J.H., Alward, W.L., Nguyen, T.D., Polansky, J.R., Sunden, S.L., Nishimura, D., Clark, A.F., Nystuen, A., and Nichols, B.E. (1997). Identification of a gene that causes primary open angle glaucoma. Science 275, 668-670.
Thanos, S., and Naskar, R. (2004). Correlation between retinal ganglion cell death and chronically developing inherited glaucoma in a new rat mutant. Experimental eye research 79, 119-129.
Waryah, A.M., Narsani, A.K., Sheikh, S.A., Shaikh, H., and Shahani, M.Y. (2013). The novel heterozygous Thr377Arg MYOC mutation causes severe Juvenile Open Angle Glaucoma in a large Pakistani family. Gene 528, 356-359.
Wiggs, J.L. (2007). Genetic etiologies of glaucoma. Archives of ophthalmology 125, 30-37.
Woodward, D.F., and Gil, D.W. (2004). The inflow and outflow of anti-glaucoma drugs. Trends in pharmacological sciences 25, 238-241.
Zhong, H., Li, J., Li, C., Wei, T., Cha, X., Cai, N., Luo, T., Yu, M., and Yuan, Y. (2012). The Prevalence of Glaucoma in Adult Rural Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye StudyPrevalence of Glaucoma in Adult Chinese Bai Nationality. Investigative ophthalmology & visual science 53, 3221-3225.


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KHAN, Luqman et al. Molecular basis of glaucoma and its therapeutical analysis in Pakistan: an overview. Biomedical Research and Therapy, [S.l.], v. 4, n. 03, p. 1210-1227, mar. 2017. ISSN 2198-4093. Available at: <>. Date accessed: 20 nov. 2017. doi:

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