Comparison of protein kinase C subtype expression between normal and aniridic human ocular surfaces: implications for limbal stem cell dysfunction in aniridia.
Frozen sections of corneoscleral buttons from normal and aniridic donors were stained with hematoxylin and periodic acid-Schiff, monoclonal antibodies AE-5 and AK-2 (to cornea-specific K3 and K12 keratins, respectively), and AM-3 (to conjunctival goblet cells) as well as with subtype-specific antibodies to seven different protein kinase C (PKC) subtypes, the signal transduction isoenzymes increasingly implicated in the regulation of cell growth and differentiation. Compared with the normal cornea, the aniridic cornea showed decreased AE-5 and AK-2 stainings, increased AM-3 staining, attenuated Bowman's membrane, invasion of new blood vessels, and limbal epithelial hyperplasia. In the normal tissue, the corneal epithelium expressed PKC alpha, lambda, and zeta; the limbal and conjunctival epithelia expressed additional PKC gamma. Conjunctival goblet cells expressed only PKC lambda. Within a given epithelium, different PKC subtypes had different cell-layer distributions. In the aniridic tissue, some of the four normally expressed subtypes were expressed in different cell layers, especially at the limbal region. PKC beta and PKC delta, which were normally weakly expressed, were markedly up-regulated. These results support the conclusion that the aniridic cornea does indeed manifest features of limbal stem cell deficiency with decreased corneal epithelial phenotype and increased conjunctival epithelial phenotype. Different capacities of proliferation and differentiation may be affected by the differential expression of PKC subtypes by different cell layers of normal ocular surface epithelia. The aberrant expression of PKC subtypes in aniridia may thus result in abnormal proliferation and differentiation noted in its ocular surface epithelia. Because limbal stem cells are the ultimate source of corneal proliferation and differentiation, we postulate that limbal deficiency in aniridia is a result of abnormal limbal stem cells.
Tseng
S C
SC
Department of Ophthalmology, University of Miami School of Medicine, Florida, USA.
Li
D Q
DQ
D000328:Adult; D005123:Eye / Q000201:enzymology*; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D007527:Isoenzymes / Q000378:metabolism*; D016850:Limbus Corneae / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism*; D012016:Reference Values; D013234:Stem Cells / Q000502:physiology*
D007527:Isoenzymes; D011493:Protein Kinase C