Non-neural regions of the adult human eye: a potential source of neurons?
OBJECTIVE
Because it is known that both melanocytes and neurons are generated from neural crest stem cells and their derived precursors, the current study was undertaken to evaluate whether adult human ocular tissues, containing melanocytes, have the capacity to generate neuronlike cells in vitro.


METHODS
Choroid and Sclera cells from adult human eyes were separately dissociated and cultivated in the presence of epidermal growth factor and 10% fetal bovine serum. No retinal pigmented epithelial cells were detected. After cell growth, cells were transferred under conditions known to induce neuronal differentiation. Cells were plated on laminin in the presence of fibroblast growth factor-2 or brain-derived neurotrophic factor.


RESULTS
Cells derived from the sclera and the choroid of 15 donors proliferated to attain a 10(8)-fold increase in the number of cells within 4 months. At each passage, groups of cells differentiated into cells with neuronal morphology, expressing neuronal markers confirmed by immunocytochemistry and RT-PCR analyses, such as beta-tubulin-III, neurofilament, and tau. Parallel to neuronlike formation, glialike cells, revealed by expression of vimentin and P0, were generated in large amounts. Although, absent from choroid and sclera tissues, nondifferentiated cells appeared in cultures.


CONCLUSIONS
The adult human eye conserves cells able to recapitulate certain neural developmental features. This observation opens new perspectives to study human neurogenesis and to provide an important source of neurons for transplantation studies in the retina and other regions of the central nervous system.
Arsenijevic
Yvan
Y
Unit of Oculogenetics, Jules Gonin Eye Hospital, Lausanne University, Lausanne, Switzerland. yvan.arsenijevic@chuv.hospvd.ch
Taverney
Nicole
N
Kostic
Corinne
C
Tekaya
Meriem
M
Riva
François
F
Zografos
Leonidas
L
Schorderet
Daniel
D
Munier
Francis
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002829:Choroid / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000166:cytology; D008875:Middle Aged; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012590:Sclera / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor