Perfusion of the juxtapapillary retina and optic nerve head in acute ocular hypertension

Chronically elevated intraocular pressure (IOP) is often associated with glaucomatous optic nerve atrophy. Impaired blood flow may play a role in the pathogenesis of this disease. We present data concerning juxtapapillary retinal and optic nerve-head blood flow during acute increases in IOP. With the combination of a laser Doppler flowmeter and a scanning-laser system (Scanning Laser Doppler Flowmeter, SLDF; Heidelberg Engineering) the perfusion of the retina and the optic nerve head was quantified and visualized. Juxtapapillary retinal and optic nerve-head blood flow was measured simultaneously by SLDF during variations in IOP induced by a suction cup in nine healthy volunteers. The ocular pressure was increased for 2 min to IOP +15 mmHg, then to IOP +30 mmHg, and finally, to IOP +45 mmHg. Ocular perfusion pressure (PP) was calculated as the mean arterial blood pressure minus the IOP. The declines in juxtapapillary retinal flow as expressed in present per 10-mmHg IOP elevation ranged from 3.6% to 14.1% (median 7.4%). Over all measurements we found a significant linear relationship between juxtapapillary retinal blood flow and PP (r = 0.55, P < 0.0001). The observed decrease in optic nerve-head blood flow with increasing IOP was significantly greater as compared with the retinal blood flow decrease (8.4%/10 mmHg versus 7.4%/10 mmHg, P < 0.05). SLDF enables the quantification and visualization of perfused capillaries of the retina and the optic nerve head in high resolution. Acute elevations of IOP led to a decreases in juxtapapillary retinal and optic nerve-head blood flow of 7.4% and 8.4%/ 10-mmHg IOP increase, respectively.     

Influence of acquisition parameters on hemodynamic measurements with the Heidelberg Retina Flowmeter at the optic disc

Asymmetrical IgG molecules are characterised by the presence of a mannose-rich oligosaccharide group in only one of the two Fab fragments, which impairs the corresponding paratope, causing such molecules to behave as univalent antibodies and therefore as antigen blockers [1-3]. During human and murine pregnancy, an increase has been detected in asymmetrical IgG molecules in serum and those bound to the placenta, which normally releases factors capable of modulating the immune response. It thus seemed of interest to investigate the effect of placental culture supernatants (PCS) on in vivo and in vitro synthesis of rat immunoglobulin IgG1, IgG2a, IgG2b and IgG2C, particularly the ratio of symmetrical and asymmetrical molecules in each isotype. The effect of PCS was determined in vivo by means of passive transfer to virgin females and in vitro by analysing the supernatants of spleen cells cultured in the presence of PCS. The results showed that neither pregnancy status nor PCS were capable of modifying serum levels of IgG2a, IgG2b or IgG2c, whereas the level of IgG1 was reduced. When PCS were added to the spleen cells cultures, an in vitro increase was observed in IgG2a, IgG2b and IgG2c production. The separation of symmetrical from asymmetrical IgG molecules was performed by affinity chromatography in Concanavalin A-Sepharose, as such lectin binds high mannose sugars present only in asymmetrical IgG molecules. It is shown that pregnancy and PCS induce an increase in IgG1 and IgG2 molecules asymmetrically glycosylated, capable of binding to ConA-Sepharose. Therefore, the placenta is capable of releasing factors which can regulate the relative proportion of asymmetrical IgG molecules and induce quantitative and qualitative modifications of the in vitro and in vivo produced antibodies.     

Medulloepithelioma of the optic nerve head

Medulloepithelioma of the optic nerve is a rare developmental tumor. We describe a 2-year-old boy with profound loss of vision associated with a visible tumor of the optic nerve head in his left eye. A clinically diagnosed retinoblastoma necessitated left eye enucleation. The histopathological diagnosis was malignant medulloepithelioma that was incompletely resected. Further tumor resection was required, and the patient received adjunctive chemotherapy and radiotherapy. Four years after treatment, the patient has neither clinical nor radiological evidence of tumor.     

Location of the fovea at the fundus in relation to the optic nerve head

BACKGROUND: Exact determination of the location of the fovea may be difficult, especially in patients suffering from macular pathology. The purpose of this study was to evaluate whether the distance between the optic nerve head and fovea in healthy eyes may be helpful in such patients. PATIENTS AND METHODS: We measured the distance between the center of the optic nerve head and the fovea in 165 healthy eyes in a horizontal and vertical direction. Results were correlated to the refractive status. RESULTS: There was a relatively high deviation between all eyes for the distance between the optic disc and the fovea (15.5 +/- 1.2 degrees [12.8 to 21.3 degrees]). There was a significant relationship between this distance and the refraction (r = 0.353, P < 0.001). Intraindividual deviation between the right and left eyes showed a markedly lower variance (0.67 +/- 0.49 degree [0.05 to 2.3 degrees]). CONCLUSION: The distance between the optic nerve head and the fovea does not allow for meaningful determination of the location of the fovea in eyes in which morphological changes have occurred. However, knowledge of this distance from the other eye of the same patient is helpful.     

Quantitative differences between the optic nerve head and peripapillary retina in low-tension and high-tension primary open-angle glaucoma

Anti-IgE antibodies directed against the Fc epsilon RI-binding region on IgE inhibit binding of IgE to IgE receptors without inducing mediator release from IgE sensitized cells. In mice these antibodies selectively reduce serum IgE, inhibit antigen induced skin reactions, cytokine production by lung Th2 cells, and pulmonary eosinophil infiltration. Clinical trials in humans reveal that such antibodies are well tolerated and reduce rhinitis symptoms and early and late phase bronchoconstriction responses. Thus interruption of the allergic cascade at the IgE antibody level with non-anaphylactogenic anti-IgE antibodies is effective and represents an attractive intervention for the treatment of allergic diseases.     

Transient neovascularisation of the frog retina during optic nerve regeneration

In conditions such as diabetic retinopathy, degenerative events in the retina are associated with neovascularisation. It is well established that a proportion of retinal ganglion cells die during optic nerve regeneration in the frog. The present study has determined whether neovascularisation takes place during this regenerative process. To do so, the pattern of blood vessels overlying the retinal ganglion cell layer was analysed in the frog Litoria (Hyla) moorei. We examined normal animals and those undergoing optic nerve regeneration following nerve crush. Blood vessels were visualised by perfusion with Indian ink and retinae were prepared as wholeamounts. In normal animals, the vascular tree was found to lie superficial to the nerve fibre layer and was more complex in regions overlying the area centralis and visual streak. After nerve crush, abnormal blood vessels transiently formed between the existing branches of the vascular tree. The new vessels were concentrated as an annulus centred on the optic nerve head and over the area centralis in midtemporal retina. The neovascularisation became most extensive between 6 and 10 weeks postcrush and disappeared by 12 weeks. The spatiotemporal sequence of neovascularisation suggests that it is triggered by accumulations of degenerating material formed as a proportion of the ganglion cells die during optic nerve regeneration.     

Progressive growth in melanocytoma of the optic nerve head

The authors describe the method of closure of laparotomic wounds by means of an atraumatic continuous PDS loop suture. Based on evaluation of a group of 166 patients they appreciate the positive aspects of the technique of this suture, in particular the speed, easy implementation and safe closure of laparotomy. As regard the sewing material, they value highly the quality of atraumatic fibres which are firm and do not irritate the tissues.     

Confocal tomographic angiography of the optic nerve head in patients with glaucoma

BACKGROUND: Essential hypertension is characterized by an impairment of endothelium-dependent vasodilatation. OBJECTIVE: To test whether antihypertensive treatment with the angiotensin converting enzyme inhibitor lisinopril can improve vasodilatation in response to endothelium-dependent agonists in essential hypertensive patients. DESIGN AND METHODS: We studied the effect of acute (6-8 h after dosing), prolonged (1 month) and chronic (12 months) lisinopril treatment on forearm blood flow response (strain-gauge plethysmography) induced in 10 hypertensive patients (aged 43.6 +/- 8.1 years, blood pressure 151.4 +/- 6.8/99.8 +/- 3.3 mmHg) by intrabrachial infusions of 0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml per min acetylcholine and 5, 15, and 50 ng/100 ml per min bradykinin, two endothelium-dependent vasodilators, and 1, 2, and 4 microg/100 ml per min sodium nitroprusside, an endothelium-independent vasodilator. At baseline, vascular response was compared with that of 10 normotensive subjects (aged 42.4 +/- 6.6 years, blood pressure 118.4 +/- 6.1/77.8 +/- 3.4 mmHg). RESULTS: Hypertensive patients had blunted (P < 0.01 or less) vasodilatations in response to infusions of acetylcholine (from 3.7 +/- 0.3 to 18.3 +/- 4.9 ml/100 ml per min) and bradykinin (from 3.7 +/- 0.4 to 15.8 +/- 2.6 ml/100 ml per min) compared with those of controls (from 3.6 +/- 0.3 to 25.3 +/- 5.2 ml/100 ml per min for acetylcholine and from 3.7 +/- 0.3 to 26.9 +/- 4.9 ml/100 ml per min for bradykinin) whereas the responses to infusion of sodium nitroprusside were similar (from 3.6 +/- 0.3 to 18.5 +/- 3.9 and from 3.6 +/- 0.3 to 16.4 +/- 1.8 ml/100 ml per min, respectively). Acute and prolonged lisinopril treatments significantly (P < 0.05 or less) improved vasodilatation in response to infusion of bradykinin (from 3.7 +/- 0.4 to 24.5 +/- 4.9 and from 3.7 +/- 0.3 to 22.1 +/- 4.9 ml/100 ml per min, respectively), but not in response to infusions of acetylcholine and of sodium nitroprusside. Chronic lisinopril treatment increased (P < 0.05) the response to infusions of not only bradykinin (from 3.5 +/- 0.5 to 27.6 +/- 5.3 ml/100 ml per min), but also of acetylcholine (from 3.5 +/- 0.5 to 27.8 +/- 8.0 ml/100 ml per min) and sodium nitroprusside (from 3.4 +/- 0.6 to 25.9 +/- 8.5 ml/100 ml per min). However, when the responses to infusions of acetylcholine and bradykinin were normalized with respect to that to infusion of sodium nitroprusside, only the vasodilatation in response to infusion of bradykinin was shown to have been increased by lisinopril treatment. CONCLUSIONS: Administration of lisinopril to patients with essential hypertension can selectively increase vasodilatation in response to infusion of bradykinin.     

Serotonin-induced constriction of ocular arteries in atherosclerotic monkeys. Implications for ischemic disorders of the retina and optic nerve head

BACKGROUND: Ischemic disorders of the retina and optic nerve head, which constitute a common cause of visual loss, are usually seen in patients with atherosclerosis. OBJECTIVE: To test the hypothesis that serotonin, which is released when platelets aggregate, may produce vasospasm in atherosclerotic monkeys and, thus, may contribute to the ischemic disorders and that short-term dietary treatment of atherosclerosis causes the propensity to vasospasm to subside. METHODS: We studied the response of retinal and posterior ciliary circulation to serotonin in 18 atherosclerotic (25 eyes) and 5 normal (8 eyes) cynomolgus monkeys. The eyes were evaluated by color fundus photography and fluorescein fundus angiography. The eyes were examined under basal conditions and, at a different time, during the intravenous infusion of serotonin. In 6 of the 18 atherosclerotic animals, the evaluation was repeated 5 to 12 months after discontinuing the atherogenic diet (ie, the regression group). RESULTS: Serotonin had no effect in normal monkeys. In 18 atherosclerotic monkeys, serotonin produced transient occlusion or delayed filling of the central retinal artery and/or posterior ciliary artery (PCA) in 9 eyes of 9 animals, involving the central retinal artery in 5, lateral PCA in 8, and medial PCA in 5, in various combinations. In 6 animals (6 eyes) of the regression group, the vasoconstrictor effect of serotonin was abolished completely, except in the medial PCA in 1 eye. CONCLUSIONS: Serotonin, in the presence of atherosclerotic lesions, can cause transient, complete occlusion or impaired blood flow in the central retinal artery and/or PCA. We speculate that this mechanism may play a role in the development of ischemic disorders of the retina and optic nerve head. Discontinuing the atherogenic diet abolished or markedly improved the serotonin-induced vasoconstriction within a few months.     

Open foramen ovale in patients with arterial vascular occlusions of the retina and optic nerve

BACKGROUND: We examined the frequency and significance of persistent foramen ovale (PFO) in patients with ocular circulatory disturbance. PATIENTS AND METHODS: Forty patients with acute arterial occlusions of the posterior bulb segment were investigated by means of transthoracic and transesophageal echocardiography (TEE). The parallel presence of cerebral ischemia was clarified on the basis of existing CCT findings and by additional HMPAO-SPECT investigation. RESULTS: PFO was identified in nine of the patients investigated. The probability of paradoxical embolism arises from further findings: eight of those with PFO (89%) showed echocardiographic signs of right heart strain, indicating previous pulmonary embolism, compared with only three of those without PFO (10%). Five of those with PFO showed a potential source of embolism, two of them with phlebothromboses in their clinical history and three with additional atrial septal aneurysm. Cardiovascular risk factors were prevalent in the group without PFO. Both groups had a mean age of approximately 60 years. Signs of cerebral ischemia were present in the SPECT or CT findings for four of the patients with PFO and nine of those without. CONCLUSIONS: From our findings, it appears highly probable that ocular arterial occlusion is caused by paradoxical embolism. PFO should be taken into account in establishing a diagnosis, including diagnosis in elderly patients.     

Platelet-derived growth factor B-chain expression in the rat retina and optic nerve: distribution and changes after transection of the optic nerve

To test the possible involvement of platelet-derived growth factor B-chain (PDGF-B) in anterograde and retrograde degenerations of the CNS neurons, we studied the changes of PDGF-B localization and its mRNA expression in the rat retina and optic nerve (ON) after unilateral ON transection, using immunohistochemistry and in situ hybridization. In the control retinas immunoreactivity for PDGF-B and its mRNA expression were localized in the retinal ganglion cells (RGCs) and the nerve fiber layer. After ON transection PDGF-B immunoreactivity in the nerve fiber layer started to decrease on post-injury day 3 or 4. Atrophic changes in the RGCs started on day 5 just after the decrease of PDGF expression, and thereafter the RGC number decreased. In the longitudinal section of the ON rostral to the transected site, swollen axons showed intense PDGF-B immunoreactivity and macrophages, and some glial cells revealed a significant increase in both immunoreactivity and hybridization signals. Based on these findings, we hypothesized that the decrease in PDGF-B in RGCs after axotomy causes the loss of RGCs, and that increased PDGF-B expression in the ON plays a role in the cascade of tissue reactions following ON transection.     

Diagnostic and therapeutic challenges. Lesions of the optic nerve head

Unilateral injection of 10 mg all-trans retinoic acid (in 1 ml of castor oil) into the early pedicle anlage of a male fallow deer resulted in accelerated growth of the cranial appendage, and altered pedicle and first antler shape on the treatment side, whereas pedicle and antler growth on the control side, injected with 1 ml of vehicle solution only, was normal. It is concluded that retinoic acid is able to alter pedicle and first antler morphogenesis, presumably by affecting the positional information of the periosteal cells covering the incipient pedicle.     

Evaluation of coexisting optic nerve head drusen and glaucoma with optical coherence tomography

OBJECTIVE: Optic nerve head drusen often make evaluation of the nerve head difficult to interpret. In addition, visual field defects are known to occur in patients with optic disk drusen, resembling glaucomatous damage. The authors report two cases of coincident optic nerve head drusen and glaucoma, in which the use of optical coherence tomography (OCT) in evaluating the nerve fiber layer was beneficial. PARTICIPANTS: Two patients with both optic nerve head drusen and glaucoma, one with primary open angle glaucoma, the other with pseudoexfoliation glaucoma were evaluated. Both patients had asymmetric optic disk drusen, with clinically visible drusen only in one eye. INTERVENTION: Ophthalmologic examination, color and red-free photography, automated Humphrey visual field testing and OCT were performed. RESULTS: Nerve fiber layer loss as measured by OCT was found to be greater than expected by the appearance of the optic nerve head and red-free photography, with visual fields consistent with findings in case 1. In case 2, visual fields were full, despite nerve fiber layer thinning seen by OCT and red-free photography. CONCLUSIONS: There can be significant nerve fiber layer thinning in patients with both glaucoma and optic disk drusen, despite the appearance of the optic nerve head in these patients. The cup margin may be obscured by the drusen, giving rise to a falsely full-appearing disk. In such cases, OCT may provide a useful means to quantitatively measure the nerve fiber layer thickness and to aid in the management of these patients by detecting nerve fiber layer thinning earlier than would otherwise be possible.     

Comparison of methods to evaluate the optic nerve head and nerve fiber layer for glaucomatous change

Depression occurs in 40% to 50% of Parkinson's disease (PD) patients. From research over the last decade, this co-occurrence appears to be more than an emotional reaction to disability. Replacement of the neurotransmitter, dopamine, benefits the PD motor functions, and the neurotransmitter, serotonin, in antidepressants, reduces depressive symptoms. However, identification of the physiological linkage between PD and depression continues to evade research efforts.     

Role of nocturnal arterial hypotension in optic nerve head ischemic disorders

OBJECTIVE: To investigate the role of nocturnal arterial hypotension, intraocular pressure (IOP) and heart rate in optic nerve head (ONH) ischemic disorders, and the effects of systemic factors and topical beta-blocker eye-drops on nocturnal arterial hypotension and heart rate. METHODS: We investigated prospectively, by 24-hour ambulatory blood pressure (BP) monitoring and diurnal curve of the IOP, 275 white patients with anterior ischemic optic neuropathy (AION - 114), normal tension glaucoma (NTG - 131) and primary open angle glaucoma (POAG - 30). RESULTS: Hourly average BP data analyses showed a significantly greater drop in mean diastolic BP (p < 0.009) at night in NTG than AION. Cases with visual field deterioration had significantly (p = 0.05) lower minimum nighttime diastolic BP. Arterial hypertensives on oral hypotensive therapy showed a significantly lower mean nighttime systolic BP (p = 0.006) and larger mean percentage drop in systolic (p < 0.0001), diastolic (p = 0.0009) and mean (p < 0.0001) BPs. Normotensives and hypertensives without therapy had no such difference. IOP showed no significant correlation with visual field deterioration in any of these conditions. Patients using beta-blocker eyedrops, compared with those not using them, had greater percentage drop in diastolic BP (p = 0.028), lower minimum nighttime diastolic BP (p = 0.072) and lower minimum nighttime heart rate (p = 0.002). CONCLUSIONS: Findings of our study suggest that nocturnal hypotension, by reducing the ONH blood flow below a crucial level during sleep in a vulnerable ONH, may play a role in the pathogenesis of AION and glaucomatous optic neuropathy (GON) and progression of visual loss in them. Thus, nocturnal hypotension may be the final insult in a multifactorial situation.     

Effect of topical timolol on tissue circulation in optic nerve head

OBJECTIVE: The aim of the present study was to determine whether removal of all amalgam restorations might significantly affect mercury levels in plasma and urine and whether the use of rubber dams might reduce patient exposure to mercury during amalgam removal. METHODS: All amalgam restorations were removed from 18 subjects during a single treatment session in which a rubber dam was used and from 10 subjects when a rubber dam was not used. All amalgam restorations were removed by the same dentist using high-speed cutting, water coolant, and high-volume evacuation. The levels of mercury in plasma and urine were analyzed both before and during the subsequent twelve months after amalgam removal. In order to determine whether removal of all amalgam restorations might cause an exposure large enough to significantly increase the mercury levels in two indicator media for mercury exposure, i.e., plasma and urine, and to determine if the removal might cause a significant decrease in the mercury levels found over time, the one-tailed, paired Students' t-test was used. For each individual, the pre-removal levels were compared with both the levels found in plasma on d 1 and in urine on d 10, and also with the levels found 1 y after removal. Furthermore, in order to examine whether the use of rubber dams had any effect on the mercury levels found after removal, the changes in the mercury levels found were compared between the groups using the Wilcoxon-Mann-Whitney rank sum test. RESULTS: After removal of all amalgam restorations, only the non-rubber dam group showed significant increases in the mercury levels found in plasma (p = 0.012) and urine (p = 0.037). However, one year later, the mercury levels in plasma and urine had sunk significantly below the pre-removal levels for both groups. When the changes in the mercury levels found were compared between the groups, the non-rubber dam group showed a significantly higher increase of mercury in plasma than the rubber dam group the day after removal (p = 0.0010). Compared to the pre-removal mercury levels in plasma and urine, the levels found 1 y after removal of all amalgam restorations were on average 52 +/- 23% (range 4-89%) lower in plasma and 76 +/- 21% (range 20-94%) lower in urine. SIGNIFICANCE: The study showed that dental amalgam had a statistically significant impact on the mercury levels found in plasma and urine in the patients tested, and that the use of a rubber dam during removal of all amalgam restorations significantly reduced the peak of mercury in plasma following removal.     

Laser scanning tomography of the optic nerve head in ocular hypertension and glaucoma

BACKGROUND: This study evaluated the ability of laser scanning tomography to distinguish between normal and glaucomatous optic nerve heads, and between glaucomatous subjects with and without field loss. METHODS: 57 subjects were classified into three diagnostic groups: subjects with elevated intraocular pressure, normal optic nerve heads, and normal visual fields (n = 10); subjects with glaucomatous optic neuropathy and normal visual fields (n = 30); and subjects with glaucomatous optic neuropathy and repeatable visual field abnormality (n = 17). Three 10 degrees image series were acquired on each subject using the Heidelberg retina tomograph (HRT). From the 14 HRT stereometric variables, three were selected a priori for evaluation: (1) volume above reference (neuroretinal rim volume), (2) third moment in contour (cup shape), and (3) height variation contour (variation in relative nerve fibre layer height at the disc margin). Data were analysed using analysis of covariance, with age as the covariate. RESULTS: Volume above reference, third moment in contour, and mean height contour were significantly different between each of the three diagnostic groups (p < 0.001). Height variation contour showed no significant difference among the three diagnostic groups (p = 0.906). CONCLUSIONS: The HRT variables measuring rim volume, cup shape, and mean nerve fibre layer height distinguished between (1) subjects with elevated intraocular pressures and normal nerve heads, and glaucomatous optic nerve heads, and (2) glaucomatous optic nerve heads with and without repeatable visual field abnormality. This study did not directly assess the ability of the HRT to identify patients at risk of developing glaucoma. It is hypothesised that the greatest potential benefit of laser scanning tomography will be in the documentation of change within an individual over time.     

Quantitative estimation of retinal nerve fiber layer height in glaucoma and the relationship with optic nerve head topography and visual field

During the evolution of normal cells into cancer cells, the occurrence of multiple mutations results in genetic instability. Mutations in DNA repair genes such as those of mismatch and excision repair predispose the carriers of these mutations to cancer by increasing the level of genomic instability. A variety of chromosome aberrations, such as abnormal ploidy, whole chromosome loss or chromosome amplification are commonly observed in cancer cells. From one cell division to the next, mammalian cells pass through an organized series of controlled events referred to as the cell cycle. In order to pursue an ordered series of molecular events, the initiation of an event during cell cycle progression is dependent on the successful completion of an earlier event. The cell cycle is divided into two major phases, namely, M(mitotic) phase and interphase. Interphase can be further divided into three distinct phases termed G1 (gap 1), S(DNA synthesis) and G2(gap2) phases (Fig. 1). Along with the machinery that promotes cell cycle progression, cells are also equipped with cell cycle checkpoints that ensure correct ordering of events in the cell cycle. The idea of "the cell cycle checkpoint" was first introduced by Hartwell and Weinert (1989) as "the arrest of a cell at a particular phase of the cycle due to a lack of appropriate signals for cell cycle progression". Until the checkpoint machinery receives the appropriate signal, the cell will not be allowed to make transition from one phase of the cell cycle to the next. Thus, the major role of checkpoint control is to minimize somatic genetic alterations and/or events affecting cellular survival. When one or more components of a cell cycle checkpoint are mutated, the chances of genetic instability during one round of the cell cycle increase accordingly with consequent acceleration of cellular evolution from the normal to the cancerous state. Therefore, mutations in checkpoint controls may predispose cells to cancer by causing genomic instability. In this review, I will focus on the potential roles of cell cycle checkpoints in the progression of malignancy.     

Neurite outgrowth from explanted Xenopus retina: an effect of prior optic nerve section

Experimental conditions are described for the in vitro study of explanted eyes from embryos of Xenopus laevis and of retinas from older larvae. When eyes are explanted from embryos of stages 25-34, a rapid outgrowth of fibroblast-like and pigment cells is observed, upon which a neuritic outgrowth is eventually superimposed. Outgrowth from the retina of later stage tadpoles (50-54) is not seen until about a week following explantation and resembles the mixed cell outgrowth observed in whole eye explants from early stage embryos. If, however, the optic nerve of an older tadpole is cut 7 days prior to explantation, a purely neuritic outgrowth is seen from the previously denervated retina within 1-3 days.