Abstract:
:Hypothesis-driven science is expected to result in a continuum of studies and findings along a discrete path. By comparison, serendipity can lead to new directions that branch into different paths. Herein, I describe a diverse series of findings that were motivated by hypotheses, but driven by serendipity. I summarize how investigations into vision-guided ocular growth in the chick eye led to the identification of glucagonergic amacrine cells as key regulators of ocular elongation. Studies designed to assess the impact of the ablation of different types of neurons on vision-guided ocular growth led to the finding of numerous proliferating cells within damaged retinas. These proliferating cells were Müller glia-derived retinal progenitors with a capacity to produce new neurons. Studies designed to investigate Müller glia-derived progenitors led to the identification of a domain of neural stem cells that form a circumferential marginal zone (CMZ) that lines the periphery of the retina. Accelerated ocular growth, caused by visual deprivation, stimulated the proliferation of CMZ progenitors. We formulated a hypothesis that growth-regulating glucagonergic cells may regulate both overall eye size (scleral growth) and the growth of the retina (proliferation of CMZ cells). Subsequent studies identified unusual types of glucagonergic neurons with terminals that ramify within the CMZ; these cells use visual cues to control equatorial ocular growth and the proliferation of CMZ cells. Finally, while studying the signaling pathways that stimulate CMZ and Müller glia-derived progenitors, serendipity led to the discovery of a novel type of glial cell that is scattered across the inner retinal layers.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Fischer AJdoi
10.1167/iovs.11-8330subject
Has Abstractpub_date
2011-09-29 00:00:00pages
7705-10, 7704issue
10eissn
0146-0404issn
1552-5783pii
52/10/7705journal_volume
52pub_type
abstract:PURPOSE:To investigate the effects of an imaginary and a visual target on torsional optokinetic nystagmus (tOKN) and directional symmetry of tOKN. METHODS:Torsional OKN was induced by a rotating random dot pattern (52 degrees in diameter, constant angular velocity: +/-30 deg/sec to +/-52 deg/sec) with an imaginary or ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:PURPOSE:This study investigated, using high-resolution magnetic resonance imaging (MRI), inferior oblique muscle (IO) position relative to the adnexa in normal controls, subjects with and without vertical strabismus following lower lid blepharoplasty, and subjects with other hypertropia. METHODS:Sagittal plane MRI was...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.14-15324
更新日期:2015-04-01 00:00:00
abstract:PURPOSE:To determine, with the use of optical coherence tomography (OCT), the peripapillary retinal nerve fiber layer (RNFL) thickness among patients with retinitis pigmentosa (RP) of different degrees of disease severity. METHODS:One eye in each of 25 RP patients was included. All patients underwent complete ocular e...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-0404
更新日期:2007-10-01 00:00:00
abstract:PURPOSE:To isolate tissue-specific gene products that contribute to corneal integrity. METHODS:A cDNA library was constructed and differentially hybridized. Cornea-specific clones were purified and further characterized. RESULTS:In this study cornea-specific gene products were isolated by differential cDNA hybridizat...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Mucins, which play important roles on the ocular surface in wettability, lubrication, and barrier function, are classified into two categories: secreted mucins and membrane-associated mucins. The most important secreted mucin on the ocular surface is MUC5AC, which is secreted by the conjunctival goblet cells. In the h...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章,评审
doi:10.1167/iovs.17-23623
更新日期:2018-11-01 00:00:00
abstract:PURPOSE:To evaluate the longitudinal variability of optic disc and retinal nerve fiber layer (RNFL) measurements obtained from optical coherence tomography (OCT), scanning laser polarimetry (SLP), and confocal scanning laser ophthalmoscopy (CSLO). METHODS:Forty-five normal and 43 glaucomatous eyes of 88 subjects were ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.07-1187
更新日期:2008-11-01 00:00:00
abstract::In vivo conjunctival epithelial healing in albino rabbits was investigated by light microscopy following both n-heptanol and trephined conjunctival wounding. Reepithelialization occurred faster following n-heptanol treatment (3 days) versus trephination (6-7 days). No goblet cells were present in the migrating epithel...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract:Purpose:To assess if ripasudil has a neuroprotective effect using mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma. Methods:Topical administration (5 μL/day) of two different concentrations of ripasudil (0.4% and 2%) were applied to EAAC1 K...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23276
更新日期:2018-04-01 00:00:00
abstract::The pattern reversal visual evoked response (VER) was recorded under conditions of artificially unbalanced visual input between two eyes, an aniseikonia induced by size lenses that alter the perceived retinal image size without changing refraction. At 3.0% aniseikonia binocular summation started to decrease, and at 5....
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00
abstract:PURPOSE:To examine the involvement of p27(KIP1) in the regulation of the proliferation of the developing corneal endothelium. METHODS:Central and peripheral corneas in C57Bl6 mice at postnatal day (P)1, P11, and 12 weeks after birth were analyzed by immunocytochemistry with anti-p27(KIP1), -p57(KIP2), and -proliferati...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-1238
更新日期:2004-07-01 00:00:00
abstract:PURPOSE:To study retinal structure in choroideremia patients and carriers using high-resolution imaging techniques. METHODS:Subjects from four families (six female carriers and five affected males) with choroideremia (CHM) were characterized with best-corrected visual acuity (BCVA), kinetic and static perimetry, full-...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10707
更新日期:2013-02-01 00:00:00
abstract:Purpose:The trabecular meshwork (TM) has an important role in the regulation of aqueous humor outflow and IOP. Regulation of the extracellular matrix (ECM) by TGFβ2 has been studied extensively. Bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) has been shown to inhibit or modulate TGFβ2 sig...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23282
更新日期:2018-04-01 00:00:00
abstract::Adaptation of saccadic magnitude and vestibulo-ocular reflex gain (VOR) was examined in six monkeys that had undergone a tenectomy of the medial and lateral recti of one eye. After the tenectomy, when the normal eye was patched, a conjugate increase in saccadic magnitude and VOR was observed in both eyes. Subsequent u...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract:Purpose:Although retinal dopamine (DA) has been long implicated in myopia development, current studies demonstrate that retinal DA levels are unaltered in C57BL/6 mice with form-deprivation myopia. This work was undertaken to explore whether and how refractive development is perturbed in this mouse strain when retinal ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.16-19543
更新日期:2016-10-01 00:00:00
abstract::Vascular luminal castings of rabbit eyes were microdissected and studied with the scanning electron microscope to delineate the anatomy of the ciliary body microvasculature. We found regional microvascular differences corresponding to well known gross topographical and ultrastructural differences that may indicate reg...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract:Purpose:To compare in vivo lamina cribrosa (LC) strains (deformations) following acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects. Methods:There were 20 healthy, 20 high-tension primary open-angle glaucoma (POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive (OHT; with...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-21982
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the rol...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.03-0756
更新日期:2004-07-01 00:00:00
abstract:Purpose:To quantify associations between microvascular density and retinal ganglion cell (RGC) axonal volume in the laminar compartments of the human optic nerve head (ONH). Methods:Eleven normal human ONHs were evaluated. Antibodies were used to label the vascular endothelium (factor VIII-related antigen/von Willebra...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-23183
更新日期:2018-03-01 00:00:00
abstract:PURPOSE:Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten Disease) is one of the most common progressive neurodegenerative disorders of childhood, resulting from autosomal recessive inheritance of mutations in the CLN3 gene. Pathologically, Batten disease is characterized by lysosomal storage of autofluorescent m...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-0143
更新日期:2004-09-01 00:00:00
abstract::Protocols for light microscopy of frog lenses that result in good visibility of cell structure from the lens surface to its nucleus are presented. The lenses are fixed in 10% neutral formalin in 0.06 M phosphate buffer and are embedded in Epon 812. Following staining of the thick sections with selected Procion dyes, e...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-09-01 00:00:00
abstract:PURPOSE:Oxygen-induced retinopathy (OIR) is a model for human retinopathy of prematurity (ROP). In OIR mice, this study determined whether blockade of β-adrenergic receptors (β-ARs) with propranolol influences retinal levels of proangiogenic factors, retinal vascularization, and blood-retinal barrier (BRB) breakdown. ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-5536
更新日期:2011-01-05 00:00:00
abstract:PURPOSE:To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa in three consanguineous Pakistani families. METHODS:Blood samples were collected and DNA was extracted. A genome-wide scan was performed by using 382 polymorphic microsatellite markers on genomic DNA from affected ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.04-1280
更新日期:2005-07-01 00:00:00
abstract::Previous investigations have shown that corneal epithelium, migrating to cover a wound, synthesizes protein and glycoprotein at a faster rate than does normal stratified epithelium. The authors have found that the maximal rate of synthesis, as indicated by the incorporation of leucine and glucosamine, occurs 16 hr aft...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To characterize the thickness profile of the corneal epithelium and the Bowman's layer across the horizontal meridian. METHODS:Forty-four eyes of 22 healthy subjects were investigated in this study. Ultra-high resolution anterior segment spectral domain-optical coherence tomography (SD-OCT) was used to assess ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.09-4748
更新日期:2011-06-01 00:00:00
abstract:Purpose:To compare the hemifield asymmetry of visual field (VF) loss in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) across all severity levels. Methods:A total of 522 eyes of 327 patients with POAG (mean age ± SD, 54.1 ± 12.4 years) and 375 eyes of 204 patients with PACG (67.3 ± 8.9 ye...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.17-22980
更新日期:2018-03-01 00:00:00
abstract::Corneas of fetal and young albino rabbits were examined by light and transmission electron microscopy. In addition, DNA and hydroxyproline content were measured in developing stroma. The results were compared with similar data from healing corneas in adult rabbits and from developing corneas of other animal species. I...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract:PURPOSE:Cilostazol, a selective inhibitor of phosphodiesterase 3, has antiplatelet aggregation and peripheral vasodilation effects. We examined the effects of cilostazol on the retinal microvascular diameter to determine its dependence on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved ...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.12-10115
更新日期:2013-02-19 00:00:00
abstract:PURPOSE:Photodynamic therapy (PDT) and the administration of compounds acting against vascular endothelial growth factor (anti-VEGF) are approved for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Experimental evidence that the combined use of both treatment opt...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.06-1224
更新日期:2007-04-01 00:00:00
abstract::The unscarified corneas of rabbits were inoculated with 50 microliter of 2-4 X 10(6) PFU/ml of herpes simplex virus, type 1 (HSV-1), McKrae strain in 10 separate experiments over a 12-month period. Sixty of 104 (57.7%) rabbits survived to postinoculation (PI) day 20. These sixty rabbits were swabbed with dacron-tipped...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1985-04-01 00:00:00
abstract::Retinal leukocyte velocity and density were estimated using blue-field entoptic imaging techniques in a controlled double-masked study to determine the relative effects of oxygen and carbon dioxide on perimacular hemodynamics in single eyes of ten normal human subjects. Mild hypoxia (inspiration of 16% O2) did not sig...
journal_title:Investigative ophthalmology & visual science
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1992-05-01 00:00:00