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Review
. 2014 Dec:129:172-82.
doi: 10.1016/j.exer.2014.10.015. Epub 2014 Oct 18.

Pathophysiology of ocular surface squamous neoplasia

Stephen Gichuhi  1 , Shin-ichi Ohnuma  2 , Mandeep S Sagoo  3 , Matthew J Burton  4
Affiliations
Review

Pathophysiology of ocular surface squamous neoplasia

Stephen Gichuhi et al. Exp Eye Res. 2014 Dec.

Abstract

The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva.

Keywords: Cancer stem cells; HIV; HPV; Limbal stem cells; Ocular surface squamous neoplasia (OSSN); Pathophysiology; Ultraviolet radiation; p53.

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Figures

Fig. 1
Fig. 1
Anatomy of the limbus.
Fig. 2
Fig. 2
Location of 352 OSSN tumours in Uganda showing most lesions occurred within the interpalpebral fissure with a higher concentration in the nasal sector.
Fig. 3
Fig. 3
A lesion of OSSN lesion in Kenya showing a circum-limbal growth pattern involving almost the entire circumference of the limbus. The margins are drawn in a black dotted line to show extension into the cornea and bulbar conjunctiva.
Fig. 4
Fig. 4
Light from a torch shining on the temporal side of the eye to illustrate that the limbus receives direct sunlight temporally which is focused nasally. Notice the glow in the nasal limbus.
Fig. 5
Fig. 5
The cell division cycle.
See this image and copyright information in PMC

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