TY - JOUR
T1 - Characterization of early retinal progenitor microenvironment
T2 - Presence of activities selective for the differentiation of retinal ganglion cells and maintenance of progenitors
AU - Hegde, Ganapati V.
AU - James, Jackson
AU - Das, Ani V.
AU - Zhao, Xing
AU - Bhattacharya, Sumitra
AU - Ahmad, Iqbal
N1 - Funding Information:
This work was supported by the Glaucoma Foundation; The Nebraska Tobacco Settlement Biomedical Research Development Fund and Research to Prevent Blindness. We thank Dr. Colin Barnstable for opsin antibody, and Kavita B. Mallya and Frank Soto Leon for their excellent technical assistance.
PY - 2007/3
Y1 - 2007/3
N2 - The maintenance and differentiation of retinal progenitors take place in the context of the microenvironment in which they reside at a given time during retinal histogenesis. To understand the nature of the microenvironment in the developing retina, we have examined the influence of activities present during the early stage of retinal histogenesis on enriched retinal progenitors, using the neurosphere model. Early and late retinal progenitors, enriched as neurospheres from embryonic day 14 (E14) and E18 rat retina, respectively, were cultured in embryonic day 3 (E3) chick retinal conditioned medium, simulating the microenvironment present during early retinal histogenesis. Examination of the differentiation and proliferation of retinal progenitors revealed that the early microenvironment contains at least three regulatory activities, which are partitioned in different size fractions of the conditioned medium with different heat sensitivity. First, it is characterized by activities, present in heat stable <30 kDa fraction, that promote the differentiation of retinal ganglion cells (RGCs), the early born neurons. Second, it contains activities, present in heat-sensitive >30 kDa fraction, that regulate the number of early born neurons and maintain the pool of retinal progenitors. Third, it possesses activities, present in heat-sensitive <30 kDa fraction, that prevent the premature differentiation of early retinal progenitors into the late born neurons. Thus, our observations demonstrate the regulatory influence of microenvironment on the maintenance and differentiation of retinal progenitors and establish neurospheres as a viable model system for the examination of such influences.
AB - The maintenance and differentiation of retinal progenitors take place in the context of the microenvironment in which they reside at a given time during retinal histogenesis. To understand the nature of the microenvironment in the developing retina, we have examined the influence of activities present during the early stage of retinal histogenesis on enriched retinal progenitors, using the neurosphere model. Early and late retinal progenitors, enriched as neurospheres from embryonic day 14 (E14) and E18 rat retina, respectively, were cultured in embryonic day 3 (E3) chick retinal conditioned medium, simulating the microenvironment present during early retinal histogenesis. Examination of the differentiation and proliferation of retinal progenitors revealed that the early microenvironment contains at least three regulatory activities, which are partitioned in different size fractions of the conditioned medium with different heat sensitivity. First, it is characterized by activities, present in heat stable <30 kDa fraction, that promote the differentiation of retinal ganglion cells (RGCs), the early born neurons. Second, it contains activities, present in heat-sensitive >30 kDa fraction, that regulate the number of early born neurons and maintain the pool of retinal progenitors. Third, it possesses activities, present in heat-sensitive <30 kDa fraction, that prevent the premature differentiation of early retinal progenitors into the late born neurons. Thus, our observations demonstrate the regulatory influence of microenvironment on the maintenance and differentiation of retinal progenitors and establish neurospheres as a viable model system for the examination of such influences.
KW - RGC
KW - extrinsic factors
KW - microenvironment
KW - niche
KW - progenitor
KW - retina
KW - rod photoreceptor
KW - stem cells
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U2 - 10.1016/j.exer.2006.11.012
DO - 10.1016/j.exer.2006.11.012
M3 - Article
C2 - 17227675
AN - SCOPUS:33846828838
SN - 0014-4835
VL - 84
SP - 577
EP - 590
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 3
ER -