干细胞生物学和再生医学 眼科

Stem Cell Biology and Regenerative Medicine in Ophthalmology

vision. As a group the population prevalence of RP is about 1:4,000, so the
estimates are that approximately 100,000 in the USA have this disease. Investigators
have identified at least 45 loci for mutations that can cause retinitis
pigmentosa, and these genes collectively account for disease in a little over half
of all patients [5–7]. Of the cloned genes for retinitis pigmentosa it is estimated
that dominant retinitis pigmentosa account for about 50 %, recessive retinitis
pigmentosa account for about 40 % and X-linked retinitis pigmentosa account for
approximately 80 % of cases, indicating that many genes remain to be identified
[6, 8]. Rods are the predominantly affected photoreceptors and dysfunction causes
night blindness and peripheral field loss beginning as early as the teenage years [9].
Disease progression leads to central acuity loss and legal blindness in the majority
of patients [10]. Classic findings on funduscopic exam include perivascular bony
spicule pigmentation, attenuated arterioles, and waxy optic disc pallor, typically
associated with vitreous cells and posterior subcapsular cataracts. However, many
of these findings may be absent in early stages of disease [11, 12]. Electroretinogram
(ERG) testing is important for diagnosis and may provide prognostic information
[10]. The genetics of retinitis pigmentosa are extremely complex with
diverse modes of inheritance [12]. Potential interventions include vitamin A therapy
and carbonic anhydrase inhibitors, but treatment options are extremely limited
in the majority of cases with no effective form of therapy. Results evaluating
vitamin A efficacy have shown limited benefit but potential risks exist with oral
vitamin A supplementation, including the risk of hepatotoxicity [13]. Carbonic
anhydrase inhibitors have shown clinical benefit in reducing macular edema and
improving visual acuity in some patients with retinitis pigmentosa [14].
Genetics
The genetics of retinitis pigmentosa are extremely complex with diverse modes of
inheritance including dominant, recessive, X-linked, mitochondrial, and digenic
forms [12]. The disease may manifest solely with visual symptoms or may be
accompanied by a constellation of systemic findings in patients with syndromic
retinitis pigmentosa. The diversity in genetic transmission and clinical presentation
is not entirely surprising given that retinitis pigmentosa constitutes a broad group of
diseases that arises from diverse biological pathways.
Retinitis pigmentosa demonstrates multiple modes of segregation [15]. Autosomal
dominant transmission occurs most frequently and accounts for 20%of retinitis
pigmentosa cases. Symptoms are generally less severe with adult-onset with variable
penetrance of symptoms. Autosomal recessive disease occurs in 13 % of cases
and is characterized by earlier onset of symptoms and severe vision loss. X-linked
recessive disease accounts for 8%of cases and has the poorest visual prognosis with
early onset and rapid progression of symptoms [12]. Visual deficits typically present
within the first decade of life and progress to partial or complete blindness by the
third or fourth decade. In approximately 20 % of nonsyndromic cases, the mode of