Proliferation Of Conjunctival Cells Research Articles

Altered retinoid metabolism gene expression in chronic Stevens-Johnson syndrome

BackgroundStevens-Johnson syndrome (SJS), a blistering disorder of the skin and mucous membrane, leads to ocular morbidity in >60% of cases. Retinoids are vital micronutrients for vision, regulating corneal and conjunctival...

Stimulatory Role of PKCα in Extracellular Regulated Kinase 1/2 Pathway in Conjunctival Goblet Cell Proliferation

To determine whether a constitutively active protein kinase C (PKC)-alpha stimulates rat and human conjunctival goblet cell proliferation through activation of ERK 1/2. Conjunctivas from rat and human were minced and goblet cells were allowed to grow. Goblet cells were serum starved and incubated with an adenovirus containing a constitutively active form of PKCalpha (Ad-myr-PKCalpha, 1 x 10(7) pfu), EGF (10(-7) M), or both. The location of myrPKCalpha was determined by immunofluorescence microscopy. Cultured goblet cells were preincubated with the PKC inhibitor calphostin C (10(-10)-10(-7) M) or the ERK 1/2 inhibitor U0126 (10(-9)-10(-6) M) before incubation with Ad-myr-PKCalpha. Cell proliferation was measured. Transduction of rat goblet cells with Ad-myr-PKCalpha did not change PKC location compared with nontransduced cells. Incubation with Ad-myr-PKCalpha caused an increase in cell proliferation by 2.5+/-0.3-fold, whereas EGF increased proliferation by 2.1+/-0.2-fold. Simultaneous addition of Ad-myr-PKCalpha and EGF did not further increase proliferation. U0126 inhibited Ad-myr-PKCalpha-stimulated proliferation a maximum of 70%. In human goblet cells, incubation with Ad-myr-PKCalpha caused an increase in cell proliferation by 2.3+/-0.3-fold, whereas EGF increased proliferation by 3.1+/-0.4-fold. Simultaneous addition of Ad-myr-PKCalpha and EGF decreased proliferation compared with either compound alone. Ad-myr-PKCalpha caused ERK 1/2 to translocate to the nucleus in rat and human cells, but the translocation was blocked by U0126. Activation of PKCalpha alone by inducing phosphorylation of ERK 1/2 and translocating it to the nucleus is necessary and sufficient to cause conjunctival cell proliferation in rat, and probably human, goblet cells.

Suppression of interleukin-1alpha-induced uveitis and inhibition of fibroblast-like cell proliferation by synthetic interleukin-1 blockers.

To treat uveitis and prolong the functional life of filtration surgery on glaucomatous eyes, some interleukin-1 (IL-1) blockers were used to inhibit IL-1-induced uveitis in rat eyes and to suppress proliferation of fibroblast-like corneal and conjunctival cells in the cell cultures, respectively. It was found in this research that the blood-aqueous barrier can be broken by IL-1alpha to allow fluorescein to enter the eyeballs and to be detected by fluorotron. The uveitis was effectively blocked by the IL-1 blockers studied in this research. It was also noted that the proliferation of fibroblast-like corneal and conjunctival cells was effectively inhibited by IL-1 blockers. The inhibition of cell growth seems to be caused primarily by the inhibition of RNA synthesis. There was a significant difference in the potency of IL-1 blockers to inhibit corneal vs. conjunctival cells. It was noted that conjunctival cells were more easily inhibited by IL-1 blockers than corneal cells. These results indicate that IL-1 blockers can suppress the proliferation of conjunctival cells at dose levels which do not affect the normal cell growth of corneal cells.