Age Related or Senile Cataract: Pathology, Mechanism and Management

Special Article - Cataract Clinical Cases and Images

Austin J Clin Ophthalmol. 2016; 3(2): 1067.

Age Related or Senile Cataract: Pathology, Mechanism and Management

Sreelakshmi V and Abraham A*

Department of Biochemistry, University of Kerala, Kariavattom, India

*Corresponding author: Annie Abraham, Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India

Received: April 04, 2016; Accepted: June 09, 2016; Published: June 15, 2016


Cataract is a serious eye disease accounts for the major cause of blindness globally. It is characterized by the loss of transparency and opacification of eye lens; an opaque lens scatters the light as it passes through it and prevents the sharpness of the image in the retina and vision becomes blurred. Cataractogenesis is associated with numerous factors acting over many years. The major reason lies behind the formation of cataract is the damage induced by free radicals, reactive oxygen/ nitrogen species to the crystalline lens. In this review, we have discussed the different events and mechanisms associated oxidative damage in the lens that gives rise to cataractogenesis, the present treatment procedures and management of cataract.

Keywords: Cataract; Eye; Lens; MAPK pathway; Oxidative stress


The visual system is the various components of eyes functioning in the process of vision by reacting to light, gain information about their environments and help to recognize the outer world by the process of visual perception and the resulting perception is called vision or sight. Vision is one of the most complex functions and it requires the cooperation of many intricate parts and the eye is made up of three coats. The outer layer ortunica externa or tunica fibrosas composed of the cornea and sclera. The middle layer or tunica media or tunica vasculosa or uvea consists of the choroid, ciliary body and iris. The inner layer or tunica interna or tunica nervosa or retinais the light-sensitive tissue layer equipped with photoreceptors. Within these coats are the aqueous humour, the vitreous body and the flexible lens. The aqueous humour is a clear fluid that is contained in two areas: the anterior chamber between the cornea and the iris and the posterior chamber between the iris and the lens. The lens is suspended to the ciliary body by the suspensory ligament (Zonule of Zinn) made up of fine transparent fibers. The vitreous body is a clear jelly that is much larger than the aqueous humour present behind the lens, and the rest is bordered by the sclera, zonule and lens. Vision begins when light rays are reflected off an object and enter the eyes through the cornea, the transparent outer covering of the eye. The cornea bends or refracts the rays that pass through a round hole called the pupil. The iris, or colored portion of the eye that surrounds the pupil, opens and closes to regulate the amount of light passing through. The light rays then pass through the lens, which actually changes shape so it can further bend the rays and focus them on the retina at the back of the eye. The retina is a thin layer of tissue at the back of the eye that contains millions of tiny light-sensing nerve cells called rods and cones, for bright light and dim light respectively. These cells in the retina convert the light into electrical impulses. The optic nerve sends these impulses to the visual cortex in the brain where a composite image is produced [1].

The lens plays a crucial role in focusing unimpeded light on the retina. Eye lens is a biconvex, transparent, elastic, avascular structure that is located just behind the iris and the pupil that receives all its nutrients from aqueous and vitreous humor. The lens is suspended in place by the zonularfibres, which attach to the lens near its equatorial line and connect the lens to a ring of muscular tissue, called the ciliary body. Changing focus to an object at a greater distance requires the relaxation of the ciliary muscle, which in turn increases the tension on the zonules, flattening the lens and thus increasing the focal distance The lens is capable of changing its shape, functions to change the focal distance of the eye so that it can focus on objects at various distances, thus allowing a sharp real image of the object of interest to be formed on the retina by the process, accommodation [2]. The lens is flexible and its curvature is controlled by ciliary muscles through the zonules.

Structurally, the lens has three main components; capsule, epithelium and fibers. The capsule is the transparent, elastic, acellular basement membrane that completely encloses the whole cell mass and is the thickest basement membrane of the body. It is made up of type IV collagen and glycosaminoglycans and its main function is in the process oaccommodation bymolding the shape of the lens in response to tension from zonules [3]. The lens epithelium represents a single sheet of cuboidal cells just beneath the capsule at the anterior surface of the lens and the intercellular communication between the adjacent epithelial cells is through gap junctions. These monolayered cells regulate most of the homeostatic functions such as nutrient and ion transport, energy metabolism etc. in the lens and maintain the transparency of the lens. The fibers are long, thin, transparent cells form the bulk of the lens that the epithelial cells elongate, divide and differentiate to form the regularly arranged lens fibres. The new lens fibres are laid on the older deeper fibres and are formed throughout the life. Lens fibers arranged in zones, the cytoplasm of the cells of superficial bow region and the newly formed lens fibres contain nucleus, mitochondria, golgi complex, rough endoplasmic reticulum and polysomes and later on, all the light scattering organelles undergo an in built suicide process that minimizes light scatter and favors transparency [4].

Lens is an unusual organelle in its composition that with extraordinarily high protein content and low water content and this enables the lens to have a refractive index considerably greater than its fluid environment. Transparency of the lens is made possible by various factors such as normal physiology of epithelial cells, regular arrangement of the lens fibers, architecture of structural and functional proteins etc. Any alteration in the normal architecture of eye lens is associated with the change in the clarity of the lens or pacification and eventually forms the cataract. It is a significant visual impairment globally and as per the latest statistical records of World Health Organization (WHO), the total number of persons with visual impairment worldwide in 2010 was 285 million and cataract is responsible for 51% of world blindness, which represents about 20 million people [5]. Cataracts may be congenital, age related or secondary. Congenital cataracts, which are present at the birth and are, the less common cataract. The main types of age-related cataracts are nuclear sclerosis, cortical and posterior subcapsular. Nuclear cataracts form in the center of the lens and cause the nucleus to become hard or sclerotic with the deposition of brown pigment. Cortical cataracts are due to the opacity lens cortex and posterior subcapsular cataracts attack the back of the lens adjacent to the capsule. Secondary cataracts are caused by diseases like glaucoma and diabetes or medications such as steroids and radiations [6]. Cataract is associated with the gradual reduction of visual quality and is accompanied by a series of pathways that associated with imbalance in oxidant-antioxidant status [7], membrane lipid peroxidation [8], defected cellular communication [9], ion imbalance [10], modification, aggregation and accumulation of proteins [11,12], lenticular cell death [13,14] inflammation [15,16] etc. Hence, based on a variety of model systems; including cell/ organ culture, animal and human studies, the review focused on exploring the various pathways relating to the pathology of cataract, current treatment modalities and therapeutic preventive measures.

Mechanism of Cataract Formation

Oxidant-antioxidant imbalance

As lens is an organelle that exposed to light throughout the life time and prone to oxidative attack induced by reactive oxygen/ nitrogen species (ROS/RNS) [17,18], it is equipped with an efficient antioxidant system for defending these oxidative/nitrosative stress. The major enzymatic antioxidants in the lens are superoxide dismutase [19], Catalase [20], glutathione peroxidase [21], glutathione reductase, glutathione-S-transferase [22], thioredoxin system etc. [23]and non-enzymatic antioxidants are reduced glutathione [24], ascorbic acid, Vitamin A, E etc. [25-28]. These antioxidants protect lens from damage induced by toxic radicals/species and oxidative stress is a metabolic state in which excessive levels of highly reactive and unstable compounds overwhelm the ability of antioxidants that quenches them. Decline in the activity of all these enzymes and molecules are reported in the formation of cataract [29,30].

Stress signaling

NFκB is a ubiquitous transcription factor activated by ROS. Normally it is located in the cytoplasm in an inactive complex with inhibitor kappa B (Iκ B) and oxidative stress induce the release of I κ B resulting in translocation of NFκB to the nucleus and it binds to DNA control elements and thus influences the transcription of specific genes associated with stress signaling and cell death. NFκBmediated pathway is reported to present in lens epithelial cells exposed to hydrogen peroxide [31] and UV stress [32] indicating its role incataractogenesis.

MAPK pathway

Mitogen-activated protein kinases (MAPKs) are serine-threonine protein kinases that play the major role in the regulation of cell proliferation, cell differentiation and cell death. MAPKs family is characterized by the conserved activation domain and specialized activation module and it comprised of extracellular signal-regulated kinases (ERK-1 and ERK-2 isoforms), the c-Jun N-terminal kinases (JNK-1, JNK-2, and JNK-3 isoforms) and the p38 MAPKs (p38α, p38β, p38γ and p38d isoforms). Each subgroup of MAPKs is activated through a cascade of sequential phosphorylation events, beginning with the activation of MAPK kinase kinases (MAP3Ks). The MAP3Ks in turn phosphorylate and activate downstream MAPK kinases (MAP2Ks), which in turn stimulate MAPK activity through dual phosphorylation on threonine and tyrosine residues within a conserved tri-peptide motif. Activated MAPKs phosphorylate diverse substrates in the cytosol and nucleus to bring about changes in protein function and gene expression that execute the appropriate biological such as proliferation, differentiation, inflammatory responses, apoptosis etc. (Figure 1). MAPK phosphatases (MKPs), which recognize the TXY amino acid motif present in MAPKs, dephosphorylate and deactivate MAPKs [33]. MAPK pathways play discrete roles in the survival and normal functioning of lenticular epithelial cells and thus the transparency of the lens [34]. Oxidative stress is a predominant extracellular stimulus that activates MAPK pathways and many reports confirms the involvement of MAPK pathway in lens epithelial cell death and cataract formation through the disorganization of gap junctions and cytoskeletal assembly in the lens [35-37].

Citation: Sreelakshmi V and Abraham A. Age Related or Senile Cataract: Pathology, Mechanism and Management. Austin J Clin Ophthalmol. 2016; 3(2): 1067. ISSN : 2381-9162