Donald Baldwin | PubMed Health

PubMed2004

Light damage induced changes in mouse retinal gene expression.

Oxidative stress plays a role in the light damage model of retinal degeneration as well as in age-related macular degeneration. The purpose of this study is to identify retinal genes induced by acute photo-oxidative stress, which may function as mediators of apoptosis or as survival factors. To accomplish this, Balb/c mice were exposed to bright cool white fluorescent light for 7 hr. Retinas were then isolated for total RNA preparation followed by Affymetrix DNA microarray analysis to compare gene expression in light damaged mice to unexposed controls. Three independent light damage experiments were carried out and statistical filters were applied to detect genes with expression changes averaging at least two-fold. Quantitative PCR was carried out to confirm altered gene expression. Seventy genes were upregulated at least two-fold immediately following light damage. QPCR confirmed upregulation of all 10 genes tested. The upregulated genes fall into several categories including antioxidants: ceruloplasmin, metallothionein, and heme oxygenase; antiapoptotic gene: bag3, chloride channels: clic1 and clic4; transcription factors: c-fos, fra1, junB, stat1, krox-24 and c/ebp; secreted signaling molecules: chitinase 3-like protein 1 and osteopontin; inflammation related genes: MCP-1 and ICAM1 and others. Upregulation of five interferon-gamma responsive genes suggests elevated interferon levels after light damage. Upregulation of three components of the AP-1 transcription factor is consistent with previous evidence implicating AP-1 in light damage pathogenesis. Four copper or iron binding proteins were upregulated, suggesting that photo-oxidative stress may affect metal homeostasis. The genes found upregulated by light damage may affect the survival of photoreceptors subjected to photo-oxidative stress.

Animals↗

PubMed2004

Gene expression profiling of porokeratosis demonstrates similarities with psoriasis.

BACKGROUND: Porokeratosis (PK) is a clinically heterogeneous entity associated with sharply demarcated, annular, or serpiginous lesions with a hyperkeratotic ridge. This disorder is associated with aberrant keratinocyte differentiation that histologically manifests as a stack of parakeratin termed the cornoid lamella; this structure represents the peripheral hyperkeratotic ridge of clinical lesions. Histologically, the keratinocytes forming the cornoid lamella demonstrate an altered differentiation program. However, the molecular basis of PK remains incompletely understood. METHODS: As a first step in characterizing PK at the molecular level, gene expression profiling was performed on a cornoid lamella isolated from a large, Mibelli-type porokeratotic lesion. As a control, gene expression profiling of peripheral uninvolved epidermis was also performed. The gene expression profile of cornoid lamellar keratinocytes was compared with similar profiles obtained from a psoriatic plaque and cutaneous squamous cell carcinoma. RESULTS: Our study demonstrates a striking similarity between the gene expression profiles of PK and psoriasis. In addition, novel markers of the porokeratotic keratinocytes were identified, including keratin 16, S-100 A8 and A9, and connexin 26. CONCLUSIONS: This study supports the hypothesis that PK is a disorder of hyperproliferative keratinocytes exhibiting similarity at the molecular level to psoriasis. Consequently, some therapeutic modalities efficacious for psoriasis may be of benefit in PK.

Gene Expression Profiling↗