Rod Reduction Research Articles

P21 - The Sequence of Locking Cap Placement through Reduction Towers during Rod Reduction in Deformity Surgery Has a Significant Effect on Strain Placed on the Construct: Use of a Novel Wireless Rod Strain Sensor

P21 - The Sequence of Locking Cap Placement through Reduction Towers during Rod Reduction in Deformity Surgery Has a Significant Effect on Strain Placed on the Construct: Use of a Novel Wireless Rod Strain Sensor

Reduction of Rod and Cone Function in 6.5-Year-Old Children Born Extremely Preterm

ImportanceThe function of rods and cones in children born extremely preterm has not yet been fully investigated.ObjectiveTo compare retinal function via full-field electroretinographic (ffERG) recordings in 6.5-year-old children born extremely preterm with children born at term.Design, Setting, and ParticipantsA subcohort study was conducted from July 1, 2010, to January 15, 2014, of the national Extremely Preterm Infants in Sweden Study, including preterm children (<27 weeks’ gestational age) and children born at term, at 6.5 years of age and living in the Uppsala health care region in Sweden. Full-field electroretinography was performed binocularly, using DTL electrodes and electroretinographic (ERG) protocols with flash strengths of 0.009, 0.17, 3.0, and 12.0 candelas (cd)/s/m2, together with 30-Hz flicker and 3.0 cd/s/m2 single-cone flash.Main Outcomes and MeasuresThe ffERG recordings were analyzed, and their associations with gestational age and retinopathy of prematurity were examined.ResultsAdequate ffERG recordings were obtained from 52 preterm children (19 girls and 33 boys; mean [SD] age at examination, 6.6 [0.1] years) and 45 children born at term (22 girls and 23 boys; mean [SD] age at examination, 6.6 [0.1] years). Lower amplitudes of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 3.0 cd/s/m2: mean difference, –48.9 μV [95% CI, –80.0 to –17.9 μV]; P=.003; the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2: mean difference, –55.7 μV [95% CI, –92.5 to –18.8 μV]; P = .004), as well as of the isolated cone response (30-Hz flicker ERG: mean difference, –12.1 μV [95% CI, –22.5 to –1.6 μV]; P = .03), were found in the preterm group in comparison with the group born at term. The implicit time of the combined rod and cone responses (the a-wave of the dark-adapted ERG protocol of 12.0 cd/s/m2) was longer (mean difference, 1.2 milliseconds [95% CI, 0.3-2.0 milliseconds]; P = .01) in the preterm group, as were the isolated cone responses (30-Hz flicker ERG: mean difference, 1.2 milliseconds [95% CI, 0.5-1.8 milliseconds]; P < .001), than in the group born at term. No association was found between the ffERG recordings and gestational age or retinopathy of prematurity in the preterm group.Conclusions and RelevanceBoth rod function and cone function were reduced in children born extremely preterm when compared with children born at term. There was no association with retinopathy of prematurity in the preterm group, which suggests that being born extremely preterm may be one of the main reasons for a general retinal dysfunction.

Range of motion, sacral screw and rod strain in long posterior spinal constructs: a biomechanical comparison between S2 alar iliac screws with traditional fixation strategies.

S1 screw failure and L5/S1 non-union are issues with long fusions to S1. Improved construct stiffness and S1 screw offloading can help avoid this. S2AI screws have shown to provide similar stiffness to iliac screws when added to L3-S1 constructs. We sought to examine and compare the biomechanical effects on an L2-S1 pedicle screw construct of adding S2AI screws, AxiaLIF, L5-S1 interbody support via transforaminal lumbar interbody fusion (TLIF), and to examine the effect of the addition of cross connectors to each of these constructs. Two S1 screws and one rod with strain gauges (at L5/S1) were used in L2-S1 screw-rod constructs in 7 L1-pelvis specimens (two with low BMD). ROM, S1 screw and rod strain were assessed using a pure-moment flexibility testing protocol. Specimens were tested intact, and then in five instrumentation states consisting of: (I) Pedicle screws (PS) L2-S1; (II) PS + S2AI screws; (III) PS + TLIF L5/S1; (IV) PS + AxiaLIF L5/S1; (V) PS + S2AI + AxiaLIF L5/S1. The five instrumentation conditions were also tested with crosslinks at L2/3 and S1/2. Tests were conducted in flexion-extension, lateral bending and axial torsion with no compressive preload. S2A1 produces reduced S1 screw strain for flexion-extension, lateral bending and axial torsion, as well as reduced rod strain in lateral bending and axial torsion in comparison to AxiaLIF and interbody instrumentation, at the expense of increased rod flexion-extension strain. Cross-connectors may have a role in further reduction of S1 screw and rod strain. From a biomechanical standpoint, the use of the S2AI technique is at least equivalent to traditional iliac screws, but offers lower prominence and ease of assembly compared to conventional sacroiliac stabilization.

Use of a plane jet for flow-induced noise reduction of tandem rods**Project partially supported by the European Union FP7 CleanSky Joint Technology Initiative “ALLEGRA” (Grant No. 308225).

Unsteady wake from upstream components of landing gear impinging on downstream components could be a strong noise source. The use of a plane jet is proposed to reduce this flow-induced noise. Tandem rods with different gap widths were utilized as the test body. Both acoustic and aerodynamic tests were conducted in order to validate this technique. Acoustic test results proved that overall noise emission from tandem rods could be lowered and tonal noise could be removed with use of the plane jet. However, when the plane jet was turned on, in some frequency range it could be the subsequent main contributor instead of tandem rods to total noise emission whilst in some frequency range rods could still be the main contributor. Moreover, aerodynamic tests fundamentally studied explanations for the noise reduction. Specifically, not only impinging speed to rods but speed and turbulence level to the top edge of the rear rod could be diminished by the upstream plane jet. Consequently, the vortex shedding induced by the rear rod was reduced, which was confirmed by the speed, Reynolds stress as well as the velocity fluctuation spectral measured in its wake. This study confirmed the potential use of a plane jet towards landing gear noise reduction.

Traumatic Atlantoaxial Rotatory Fixation (AARF) with Odontoid Fracture, Case report

Introduction Atlantoaxial rotatory fixation (AARF) is also known as rotatory subluxation, rotatory displacement, rotary deformity, rotational subluxation, and is characterized by incomplete dislocation of the inferior atlantal and superior axial articular facets.1 AARF in combination with odontoid fracture is an extremely rare injury.2–6 Atlantoaxial injuries can be classified according to Fielding 1 or White and Panjabi7 classification. The management of this combination is a matter of debate. 1,8,9 Material and Methods We present a case of a 78 years old woman who sustained a fall on the ground from a couch directly on her forehead, resulting in atlantoaxial dislocation with type II odontoid fracture accompanied with left sided hemiparesis ASIA type C. Results After failure of closed reduction, the treatment plane was to achieve reduction under anesthesia and C1–2 fusion, but again reduction was not possible. Occipitocervical fusion to C3 was done to have better stability in osteoporotic bone. Successful reduction was achieved during rod reduction from the occiput to C2 pedicle screw and C3 lateral mass screw. Cervical collar was advised for 3 months, and good fusion and improvement of the neurological status to ASIA type D was achieved after 6 month. Conclusion AARF with Odontoid Fracture is a rare combination and reduction may be impossible. Occipitocervical fusion is a good option in such case as C1–2 reduction is a prerequisite for transarticular screw. C2 pedicle screw offers good purchase even in osteoporotic bone which enabled reduction after rod repositioning. References Fielding JW, Hawkins RJ. Atlanto-axial rotatory fixation. (Fixed rotatory subluxation of the atlanto-axial joint). J Bone Joint Surg Am 1977;59(1):37–44 Born CT, Mure AJ, Iannacone WM, DeLong WG Jr. Three-dimensional computerized tomographic demonstration of bilateral atlantoaxial rotatory dislocation in an adult: report of a case and review of the literature. J Orthop Trauma 1994;8(1):67–72 Jones RN. Rotatory dislocation of both atlanto-axial joints. J Bone Joint Surg Br 1984;66(1):6–7 Moore KR, Frank EH. Traumatic atlantoaxial rotatory subluxation and dislocation. Spine 1995;20(17):1928–1930 Robertson PA, Swan HA. Traumatic bilateral rotatory facet dislocation of the atlas on the axis. Spine 1992;17(10):1252–1254 Wise JJ, Cheney R, Fischgrund J. Traumatic bilateral rotatory dislocation of the atlanto-axial joints: a case report and review of the literature. J Spinal Disord 1997;10(5):451–453 White AA III, Panjabi MM. The clinical biomechanics of the occipitoatlantoaxial complex. Orthop Clin North Am 1978;9(4):867–878 Schmidek HH, Smith DA, Sofferman RA, Gomes FB. Transoral unilateral facetectomy in the management of unilateral anterior rotatory atlantoaxial fracture/dislocation: a case report. Neurosurgery 1986;18(5):645–652 Crockard HA, Rogers MA. Open reduction of traumatic atlanto-axial rotatory dislocation with use of the extreme lateral approach. A report of two cases. J Bone Joint Surg Am 1996;78(3):431–436

Deiodinase knockdown affects zebrafish eye development at the level of gene expression, morphology and function

Retinal development in vertebrates relies extensively on thyroid hormones. Their local availability is tightly controlled by several regulators, including deiodinases (Ds). Here we used morpholino technology to explore the roles of Ds during eye development in zebrafish. Transcriptome analysis at 3 days post fertilization (dpf) revealed a pronounced effect of knockdown of both T4-activating Ds (D1D2MO) or knockdown of T3-inactivating D3 (D3bMO) on phototransduction and retinoid recycling. This was accompanied by morphological defects (studied from 1 to 7 dpf) including reduced eye size, disturbed retinal lamination and strong reduction in rods and all four cone types. Defects were more prominent and persistent in D3-deficient fish. Finally, D3-deficient zebrafish larvae had disrupted visual function at 4 dpf and were less sensitive to a light stimulus at 5 dpf. These data demonstrate the importance of TH-activating and -inactivating Ds for correct zebrafish eye development, and point to D3b as a central player.

Treatment of fixed atlantoaxial dislocation and basilar invagination with C1-2 screw and rod reduction and fixation technique

To introduce a novel technique of reducing fixed atlantoaxial dislocation (FAAD) and basilar invagination (BI) with C1-C2 screw and rod system. From January 2009 to December 2011, 26 patients of FAAD and BI were reduced successfully with an insertion of C1 lateral mass and C2 pedicle/pars screw and rod system. The cohort had 17 females and 9 males. And their most common presenting symptoms were extremity muscle weakness, restricted neck movement and paresthesia. All of them achieved effective reduction. Among them, 18 attained complete reduction and 8 partial reduction (over 60% extent of reduction). The mean atlanto-dental interval (ADI) value was 2.1 mm postoperatively versus 8.8 mm preoperatively (t = 21.1, P < 0.01) . All of them had relieved compression of dura and medulla oblongata and cervical cord. All clinical symptoms improved. One case had pulmonary infection while another case delayed healing of incision. Both recovered well after symptomatic treatments. Bony fusion reached 100% during a mean follow-up period of 22 months. The C1-C2 screw and rod system may achieve effective reduction and fixation for FAAD and BI. Capable of preserving atlanto-occipital joints in patients without atlas assimilation, this procedure provide more solid immobilization than occipitocervical fusion in those with atlas assimilation.

Effects of rod reduction on pedicle screw fixation strength in the setting of Ponte osteotomies

Background contextThe use of a rod reduction device can have deleterious consequences on pedicle screw pullout strength (POS) in the thoracic spine. However, posterior-only osteotomies in the thoracic spine are often performed to improve flexibility of the spine and offset forces of deformity correction maneuvers. PurposeTo investigate the effect on pedicle screw POS caused by the rod reduction technique in the presence of facet osteotomies in the thoracic spine. Study design/settingThe study is a biomechanical study using human cadaveric spine specimens. MethodsThoracic Ponte osteotomies were performed on 3 thoracic levels in 15 cadaveric specimens. The right rod was contoured with a 5-mm residual gap at the middle level and was reduced using a rod reduction device. On the left side (paired control), a rod with no mismatch was placed. Biomechanical testing was performed with tensile load to failure “in line” with the screw axis and POS measured in Newtons (N). ResultsAfter rod reduction, thoracic pedicle screw POS was significantly decreased (40%) compared with the control (419±426 N vs. 708±462 N, p=.002) and remained statistically significant after adjusting for bone mineral density (BMD) (p=.05). Eleven (73%) of the pedicle screws had visible pullout/failure during the reduction attempt and occurred irrespective of BMD. ConclusionsDespite thoracic Ponte osteotomies and increased flexibility of the spinal segments, the rod reduction device still significantly decreased pedicle screw POS, typically resulting in outright failure of the screw-bone interface. Therefore, rod reduction technique of any kind should be performed with caution as it frequently results in suboptimal pedicle screw fixation.

Experimental and Numerical Study on Aerodynamic Noise Reduction of Cylindrical Rod with Bionic Wavy Surface

Inspired by the non-smooth structure of the leading edge of owls wing,a bionic wavy cylindrical surface is proposed in this paper to reduce the aerodynamic noise of a cylindrical rod. The effects of bionic wavy surface on the aerodynamic and aeroacoustic performance of the cylinder are investigated by wind tunnel and numerical simulation. The fluctuating pressure of the smooth cylinder and the bionic wavy surface cylinder are tested by pulsating pressure sensors in FD-09 low speed wind tunnel of China Aerospace Aerodynamics Research Institute. The fluctuating pressure of the bionic wavy surface cylinder is significantly lower than that of the smooth cylinder. We used the software ANSYS FLUENT to research the effect of the bionic wavy surface on the aerodynamic characteristics and aerodynamic noise of a cylinder by the Large Eddy Simulation (LES) and the Ffowcs Williams and Hawkings (FW-H) equation. Compared with the smooth cylinder, the aerodynamic noise of the bionic wavy cylinder is reduced by 6.7dB. A study of the relationship between the fluctuating lift and the aerodynamic noise size is conducted. We found that the sound pressure level of the wavy surface cylinder is significantly lower when the lift fluctuation amplitude decreased. Bionic wavy surface can effectively restrain the separated shear layer transition to turbulence. The frequency of vortex shedding which causes the lift fluctuations is reduced, so the aerodynamic noise of the circular cylinder is reduced. Keywords: bionics, cylindrical rod, wavy surface, aerodynamic noise, flow control

The Biomechanical Consequences of Rod Reduction Following Thoracic Ponte Osteotomy and Lumbar Facetectomy

The Biomechanical Consequences of Rod Reduction Following Thoracic Ponte Osteotomy and Lumbar Facetectomy

The biomechanical consequences of rod reduction on pedicle screws: should it be avoided?

Background contextRod contouring is frequently required to allow for appropriate alignment of pedicle screw-rod constructs. When residual mismatch is still present, a rod persuasion device is often used to achieve further rod reduction. Despite its popularity and widespread use, the biomechanical consequences of this technique have not been evaluated. PurposeTo evaluate the biomechanical fixation strength of pedicle screws after attempted reduction of a rod-pedicle screw mismatch using a rod persuasion device. MethodsFifteen 3-level, human cadaveric thoracic specimens were prepared and scanned for bone mineral density. Osteoporotic (n=6) and normal (n=9) specimens were instrumented with 5.0-mm–diameter pedicle screws; for each pair of comparison level tested, the bilateral screws were equal in length, and the screw length was determined by the thoracic level and size of the vertebra (35 to 45 mm). Titanium 5.5-mm rods were contoured and secured to the pedicle screws at the proximal and distal levels. For the middle segment, the rod on the right side was intentionally contoured to create a 5-mm residual gap between the inner bushing of the pedicle screw and the rod. A rod persuasion device was then used to engage the setscrew. The left side served as a control with perfect screw/rod alignment. After 30 minutes, constructs were disassembled and vertebrae individually potted. The implants were pulled in-line with the screw axis with peak pullout strength (POS) measured in Newton (N). For the proximal and distal segments, pedicle screws on the right side were taken out and reinserted through the same trajectory to simulate screw depth adjustment as an alternative to rod reduction. ResultsPedicle screws reduced to the rod generated a 48% lower mean POS (495±379 N) relative to the controls (954±237 N) (p<.05) and significantly decreased work energy to failure (p<.05). Nearly half (n=7) of the pedicle screws had failed during the reduction attempt with visible pullout of the screw. After reduction, decreased POS was observed in both normal (p<.05) and osteoporotic (p<.05) bone. Back out and reinsertion of the screw resulted in no significant difference in mean POS, stiffness, and work energy to failure (p>.05). ConclusionsIn circumstances where a rod is not fully seated within the pedicle screw, the use of a rod persuasion device decreases the overall POS and work energy to failure of the screw or results in outright failure. Further rod contouring or correction of pedicle screw depth of insertion may be warranted to allow for appropriate alignment of the longitudinal rods.

Reversing the concept: correction of adolescent idiopathic scoliosis using the convex rod de-rotation maneuver

To show the radiological results of adolescent idiopathic scoliosis (AIS) patients treated with posterior fusion using all-pedicle-screw construct with correction carried out using a convex rod reduction technique. Between October 2004 and June 2007, 42 AIS patients were treated with posterior fusion using all-pedicle-screw construct with correction done through the convex side. Two patients were lost to follow-up and were not included in the study. Forty patients had a minimum follow-up of 2years. Patients were evaluated for the deformity correction in coronal and sagittal planes and for spinal balance. The mean preoperative Cobb angle of the major curve and secondary minor curves was 60° and 41°, respectively. Immediate postoperative mean Cobb angle of the major curve and secondary minor curves was 17° and 13°, respectively. Postoperative 2-year average major curve loss of correction was 7%. Postoperative 2-year average minor curve loss of correction was 5%. Preoperative thoracic kyphosis of 28° was changed to 22° in 2-years follow-up. The loss of thoracic kyphosis was most noted in hyperkyphotic patients. The correction of AIS by convex-sided pedicular screws yields a coronal correction comparable to what is described in the literature for segmental concave-sided screws.

The Biomechanical Consequences of Rod Reduction on Pedicle Screws: Should it be Avoided?

Rod contouring is frequently required to allow for appropriate alignment of pedicle screw-rod constructs. When residual mismatch remains after contouring, a rod persuasion device is often utilized to reduce the rod to the pedicle screw head. Despite its popularity and widespread use, the biomechanical consequences of this rod reduction technique have not been evaluated.

Reverse ageing in hot-rolled high-carbon steel wire rod

Effects of ageing time on area reduction of hot-rolled high-carbon steel wire rods were studied. Tensile testing and X-ray study of as-rolled wire rods were carried out. Gleeble simulation and hydrogen content determination were also conducted. The results show that the reduction of area increases with ageing time at room temperature and the UTS remain unchanged which are contrary to normal ageing or strain ageing. In normal ageing, the ductility drops and the yield strength increases. In this study, the Gleeble simulation and X-ray data support that the transformation from pearlite to austenite is normal and there is no evidence of retained austenite or martensitic transformation in the steel. The hydrogen content drops as the time passes. The drop is rapid in first few days and this drop increases the ductility in rolled high-carbon wire rod. Hydrogen reduces the cohesive strength and the pressure generated due to transformation of atomic hydrogen-to-molecular state combines with tensile stress and causes cleavage or mixed type of fracture.

Nephropathic Cystinosis: Posterior Segment Manifestations and Effects of Cysteamine Therapy

Cystinosis is a rare autosomal recessive lysosomal storage disorder characterized by the intracellular accumulation of cystine. Treatment involves intracellular cystine depletion with oral cysteamine. A wide spectrum of ocular pathologic features has been associated with nephropathic cystinosis. We used the largest documented cohort of patients in the world to study the posterior segment manifestations associated with infantile nephropathic cystinosis and to determine retrospectively the effect of chronic oral cysteamine therapy on the frequency of these abnormalities. Cross-sectional study of a series of patients. Two hundred eight patients with infantile nephropathic cystinosis were studied at the National Institutes of Health between 1976 and 2004. All patients underwent an ophthalmic evaluation. Patients older than 11 years also underwent Humphrey static perimetry, and electrophysiological testing was performed when possible. Visual acuity, retina findings, visual fields, and electroretinographic (ERG) findings. Pigmentary changes with retinal pigment epithelial mottling, seen as early as infancy, were the most common posterior segment manifestations. Moderate to severe constriction of the visual fields, as well as moderate to severe reduction of rod- and cone-mediated ERG responses, was seen in older patients. The frequency of retinopathy correlated directly with time not receiving oral cysteamine therapy and inversely with time receiving oral cysteamine therapy. Infantile nephropathic cystinosis has posterior segment complications that can contribute to significant visual handicap. Early initiation of oral cysteamine therapy can reduce the frequency of posterior segment complications in cystinosis patients.

Colonization of Aedes aegypti midgut by the endosymbiont-bearing trypanosomatid Blastocrithidia culicis

Monoxenous trypanosomatids inhabit invertebrate hosts throughout their life cycle. However, there have been cases of HIV-positive patients who have presented opportunistic infections caused by these protozoa, offering new perspectives to the study of interactions between monoxenics and hematophagous insect vectors. Some monoxenous trypanosomatids present a symbiotic bacterium in the cytoplasm, which seems to promote biochemical and morphological changes in the host trypanosomatids, such as alterations in plasma membrane carbohydrates and the reduction of the paraxial rod. In this work, we investigated the colonization of Aedes aegypti with Blastocrithidia culicis, an endosymbiont-bearing trypanosomatid. B. culicis remained in the insect digestive tract for 38 days after feeding. Optical microscopy analysis revealed an infection process characterized by a homogenous distribution of the trypanosomatid along the midgut epithelium; no preferential interaction of protozoa with any cell type was observed. Ultrastructural analysis showed that during the colonization process, trypanosomatids interacted mainly with midgut cells through their flagellum, which penetrates the microvilli preferentially near the tight junctions. Prolonged infections promoted insect midgut degradation, culminating with the arrival of protozoa in the hemocel. By demonstrating B. culicis colonization in a bloodsucking insect, we suggest that vector transmission of monoxenous trypanosomatids to vertebrate host may occur in nature.

Highly concentrated Si1-xCx alloy with an ordered superstructure.

An ordered Si-C alloy was observed in the products resulting from thermal reduction of molybdenum disilicide heating rods. High-resolution transmission electron microscopy measurements indicate that the Si1-xCx alloy with x approximately 25% is pure, single crystalline, and possesses a superlattice structure. The superlattice periodicity occurs along the diamond [001] direction and corresponds to the quintupling of the primary (002) periodicity. The possible growth mechanism is discussed. The Mo element is likely to play a crucial role in the growth process of the Si1-xCx alloy, since it can both reduce the energy required for breaking up C clusters and contribute to surface modification, which are of great benefit to enhance the carbon concentration and induce an ordered structure.

Larger absolute photonic band gap in two-dimensional air–silicon structures

We investigate different aspects of the absolute photonic band gap (PBG) formation for two-dimensional photonic crystals, consisting of air rods drilled into silicon. Specifically, square lattices of square and circular rods are considered. The lattice symmetry, shape and orientation of the rods affect the photonic gap parameters. A symmetry reduction by addition of a smaller different shaped rod into the center of the lattice unit cell can produce significantly larger band gap. Combining the symmetry reduction and rotation of the noncircular rods yields the greatest improvements in the size of absolute band gap. We discuss the maximization of the absolute PBG width as a function of lattice parameters and the practical fabrication feasibility of these optimized structures.

ERG Abnormalities in Relation to Histopathologic Findings in Vitiligo Mutant Mice

The vitiligo,mivit, mutation has several prenatal and perinatal effects on development of the retinal pigment epithelium, and later, leads to extensive, progressive degeneration of photoreceptor cells in the neural retina of homozygous affected mice. The aim of the present study was to determine by functional criteria how early can abnormalities be detected in the neural retina. Electroretinograms (ERGs) were correlated with histopathological findings in the same animals. Congenic homozygous mutants, heterozygotes, and homozygous wild-type mice were studied at 2, 3, 6, 24 and 56 weeks of age, the same animals being tested serially at the three older time points. The nontested eye of each animal was embedded in Epon and sectioned at 1 μm for light microscopic study. ERG recordings from vitiligo homozygotes differed from heterozygous and wild-type mice, but the latter two groups did not differ from each other. As early as two weeks of age, homozygous mutants showed a significant reduction of rod dominated maximum ERG a-wave and b-wave amplitude. ERG b-wave sensitivity (σ) was significantly reduced, and ERG implicit times were delayed for homozygous mutants at 3 (a-wave) and 6 (b-wave) weeks of age. This is the first study to report reduced and delayed ERG a-waves and b-waves in this animal model, like the early functional abnormalities in human retinitis pigmentosa, and also the first to show short and disoriented rod outer segments, beginning retinal separation from the pigment epithelium, and a few macrophage-like cells already present in the subretinal space at 2 weeks of age (in three of four homozygous mutant eyes examined). Given these early functional and structural abnormalities in the neural retina, it remains to be determined whether themigene targets the retinal pigment epithelial cell, the photoreceptor cell, or both.

Correction of retinal abnormalities found in albinism by introduction of a functional tyrosinase gene in transgenic mice and rabbits

The factors that regulate normal retinal development remain obscure. However, it is known that elements in the retinal pigment epithelium are critical. When melanin is absent there is a reduction in rods, the central retina fails to develop fully and there is a systematic distortion in the chiasmatic projection to the brain. It has been demonstrated using transgenic mice that the chiasmatic abnormality is controlled by the tyrosinase gene, which is the key enzyme in melanin synthesis. Here we examine whether the two retinal deficits are regulated by this gene. We have examined the distribution of photoreceptors in an albino mouse strain in which a functional tyrosinase gene has been inserted and compared these transgenics with albino and wild type mice. In albinos, rod photoreceptors were reduced by approximately 30%, but were normal in the transgenics. Cone numbers were unchanged. Cell density in the ganglion cell layer was examined in transgenic rabbits, in which albinism had also been rescued with the tyrosinase gene. Normal rabbits have a steep gradient in cell density between central and peripheral retina. Cell density was abnormally low in the central retina in albinos, but normal in the transgenics. Hence, the tyrosinase gene is responsible for each of the retinal deficits associated with albinism. However, it is not clear whether this is due to the absence of melanin or whether the key agent is an associated cell product.