This model is highly relevant to clinical manifestations of CRAO and is an ideal animal model for research. These findings indicate the activation of the mitochondrial pathway in ischemic retina induced by CRAO. The model provides a better understanding of ischemia-induced retinal apoptosis. Antiapoptosis therapy directly targeting the mitochondrial pathway in CRAO or other retinal ischemic diseases may be beneficial.
Background
Retinitis pigmentosa (RP) is a progressive inherited retinal disease with great interest for finding effective treatment modalities. Stem cell-based therapy is one of the promising candidates. We aimed to investigate the safety, feasibility, and short-term efficacy of intravitreal injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in participants with advanced stage RP.
Methods
This non-randomized phase I clinical trial enrolled 14 participants, categorized into three groups based on a single dose intravitreal BM-MSC injection of 1 × 106, 5 × 106, or 1 × 107 cells. We evaluated signs of inflammation and other adverse events (AEs). We also assessed the best corrected visual acuity (BCVA), visual field (VF), central subfield thickness (CST), and subjective experiences.
Results
During the 12-month period, we noticed several mild and transient AEs. Interestingly, we found statistically significant improvements in the BCVA compared to baseline, although they returned to the baseline at 12 months. The VF and CST were stable, indicating no remarkable disease progression. We followed 12 participants beyond the study period, ranging from 1.5 to 7 years, and observed one severe but manageable AE at year 3.
Conclusion
Intravitreal injection of BM-MSCs appears to be safe and potentially effective. All adverse events during the 12-month period required observation without any intervention. For the long-term follow-up, only one participant needed surgical treatment for a serious adverse event and the vision was restored. An enrollment of larger number of participants with less advanced RP and long-term follow-up is required to evaluate the safety and efficacy of this intervention.
Trial registration
ClinicalTrials.gov, NCT01531348. Registered on February 10, 2012
We studied 247 Japanese males with congenital deutan color-vision deficiency and found that 37 subjects (15.0%) had a normal genotype of a single red gene followed by a green gene(s). Two of them had missense mutations in the green gene(s), but the other 35 subjects had no mutations in either the exons or their flanking introns. However, 32 of the 35 subjects, including all 8 subjects with pigmentcolor defect, a special category of deuteranomaly, had a nucleotide substitution, A؊71C, in the promoter of a green gene at the second position in the red͞green visual-pigment gene array. Although the ؊71C substitution was also present in color-normal Japanese males at a frequency of 24.3%, it was never at the second position but always found further downstream. The substitution was found in 19.4% of Chinese males and 7.7% of Thai males but rarely in Caucasians or African Americans. These results suggest that the A؊71C substitution in the green gene at the second position is closely associated with deutan color-vision deficiency. In Japanese and presumably other Asian populations further downstream genes with ؊71C comprise a reservoir of the visual-pigment genes that cause deutan color-vision deficiency by unequal crossing over between the intergenic regions.
The 15% mortality rate in our patients is slightly higher than that reported in developed countries. Delayed diagnosis and treatment is the main cause of avoidable deaths. Improving education of both clinicians and parents would increase survival rates in this potentially fatal disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.